INDEX

Preface.

Introduction.

PART a

Viruses: Common Characteristics.

1. Virus: Sendai RNA virus. (SeV), (SEND)
2. Virus: Rous RNA sarcoma. (RSV)
3. Virus: Adenovirus. DNA (MAV-1, MAD-1&2, FAV-1 to 8, TAV-1 & 2)
4. Virus: Cytomegalovirus. (CMV, MCMV, HHV-5, HCMV)
5. Virus: Encephalomyocarditis. -- RNA. (EMCV, TBEV)
6. Virus: Ectromelia, the DNA poxvirus of mice. (ECTV)
7. Virus: HI (Toolan) virus. (THV)
8. Virus: Sialodacryoadenitis coronavirus. RNA (SDAV)
9. Virus: Hantavirus. RNA - (HFRS, KHF, EHF, NE)
10. Virus: Coronaviruses. RNA (RCV, SDAV, PRC, IBV, MERS-COV, HCoV-, SARS-COV)

    PART b

11. Virus: Avian leukosis. (ALV/ALV-J) retrovirus
12. Virus: Rotaviruses. RNA (EDIM, ADRV, CAL) - gastroenteritis
13. Virus: Lymphocytic choriomeningitis. RNA (LCMV)
14. Virus: Theiler's encephalomyelitis. RNA (TMEV, GD VII, SAFV, VHEV)
15. Virus: Kilham rat parvovirus. DNA (RV, KRV, RPV-1, RPV-2, MKV)
16. Virus: Newcastle disease. RNA (NDV)
17. Virus: Anellovirus. DNA (TTV, TTMV, TMDV, PRA, SAV, SealAV, ZcAV)
18. Virus: Mouse Minute Parvovirus. DNA (MVM(p), MVM(i), RV, PVR-1)
19. Virus: Polyoma virus. DNA (MPV, BKV, JCV, SV40, PyV, RPV, BFD ..)
20. Virus: Norovirus. RNA (NoV, SRSVs)

PART c

• Virus: Chickenpox, varicella zoster virus (VZV)
• Virus: Hepatitis -- Liver inflammation -- 5 viruses.
• Virus: Measles, Morbilliviruses, RNA (MV, RPV)
• Virus: Reovirus type 3. RNA (ARV, MRV, BRV, NBV, RRV, )
• Virus: Pneumonia, DNA/RNS - Influenza, Syncytial, Parainfluenza. (RSV, PIV, )

PART d

Parasite: Chlamydial intracellular bacterial virus.

Bacteria: Tularemia -- Intracellular bacterium.

- Virus : Murine retroviruses. DNA (MuLV, HIV.., SMRV, MoMLV, HTLV, BLV)

- Virus : Quailpox Virus, DNA (AVP, )

Parasite: Borrelia (Deer/Bear tick)

-Focus-: Monographs on Toxins and Enhancers.

Virus: Avian leukosis. (ALV/ALV-J) retrovirus INDEX
https://en.wikipedia.org/wiki/Avian_sarcoma_leukosis_virus

LINK 2: https://www.idexx.com/.../avian-leukosis-virus.html
LINK 3: http://www.thepoultrysite.com/../avian-leukosis-...group/ (2014)
LINK 4: http://www.chickenvet.co.uk/.../avian-leukosis/index.aspx (2015)
LINK 5: Emerging Infectious Diseases -- Vol. 16, No. 10, October 2010

Avian leukosis virus belongs to a family of viruses called retroviruses.
In this family of viruses are bovine leukosis (affecting cattle), feline leukosis (affecting cats) and HIV.

Avian Leukosis infects the white blood cells, these are the cells that the body uses to fight infections, which leads to two main affects.

Firstly, the virus damages the infected white blood cells so the bird cannot fight off diseases, this can lead to your chicken developing other infections such as Respiratory Disease and Coccidiosis. When these infections are treated by your vet you will find the birds do not recover as well as expected.

Secondly, the virus eventually goes on to form tumours in the internal organs of the chicken such as the liver, spleen, kidneys, reproductive organs and bones.

Lymphoid leukosis, the most common manifestation of the avian leukosis/sarcoma group of viruses, produces a variety of neoplastic diseases, including erythroblastosis, myelocytomatosis, myeloblastosis and others. Not all infected birds will develop tumors. Infection can occur horizontally from bird to bird by direct or indirect contact, or vertically from an infected hen to her eggs as virus is shed into the albumin of the egg. In addition, vertical transmission may occur from virus incorporated in the DNA of a germ cell. Viremia in the hen is strongly associated with the transmission of virus congenitally. Enzyme immunoassays have proven efficacious in the detection of both leukosis antibody and antigen.

The first filterable disease agent that we now classify as a retrovirus (lentivirus) was the equine infectious anemia virus. In 1908, Ellerman and Bang (1908) of Denmark described a form of erythroleukemia in chickens that could be passed as a filterable agent. It represented the first example of an avian leukemia virus (ALV), but the malignant nature of leukemia was not generally recognized, and this important discovery did not have the impact of RSV. Even Rous's findings were not at first thought to be of particular interest because a solid tumor in a bird was not considered to be a suitable model for mammalian cancer. Viruses were thought to cause acute diseases that would rapidly appear in the majority of infected individuals. That paradigm was different from our modern knowledge of viral oncogenesis and of persistent infections with long latency periods.

A complex of viral diseases with various manifestations such as lymphoid leukosis, myeloblastosis (see Sero-type J), erythroblastosis, osteopetrosis, myxosarcomas, fibrosarcomas, other tumours. It affects chickens worldwide with susceptibility varying considerably among different strains and types of stock - egg layers are generally more susceptible to lymphoid leukosis.

Morbidity is low but mortality high.
Mortality tends to be chronically higher than normal for a prolonged period.
Egg production is somewhat reduced. There may be increased susceptibility to other infectious diseases due to damage to the immune system. Vertical transmission is most important by infection of the egg white in infected breeders (who are long-term carriers), lateral transmission is poor but infection may occur by the faecal-oral route, especially in young birds. In lymphoid leukosis the incubation period is about 4-6 months; it may be as short as 6 weeks for some of the other manifestations. The causative viruses are rapidly inactivated at ambient temperature and on exposure to most disinfectants.

Signs
• Depression.
• Emaciation.
• Loss of weight.
• Persistent low mortality.
• Enlargement of abdomen, liver or bursa.
• Many are asymptomatic.

Initially, the chickens may appear to have a minor respiratory infection or diarrhoea; however even with treatment the birds often fail to improve and the affected birds often become dull and lose a lot of weight. Eventually if not euthanized these birds die. In some cases Avian Leukosis causes bone tumours to form in the legs leading to thickened bowed legs.

Post-mortem lesions
Focal grey to white tumours, initially in the bursa, then liver, spleen, kidney etc.
Liver may be very large. Microscopic - cells lymphoplastic.

... cases of avian leukosis virus subgroup J (ALV-J) infection and tumors in commercial layer chickens and breeders of egg-type chickens have been emerging in the People's Republic of China. ALV-J was first isolated from meat-type chickens with myeloid leukosis in 1988. Although egg-type chickens have been experimentally infected with ALV-J to induce tumors, field cases of ALV-J infection and tumors in commercial layer chickens were not found worldwide until 2004.

ALV-J has recently been found to have induced various tumors and caused production problems in commercial layer flocks and local chicken breeds in China. Many field cases of ALV-J infection and tumors have occurred in 15- to 29-week-old egg-type chickens in several provinces. Affected flocks had dramatically reduced egg production and hemorrhage in the skin surrounding the phalanges and feather follicles. Some birds had gray-white nodules in the liver, spleen, or kidneys, and liver and spleen were enlarged up to several times their normal size. Morbidity rates for some flocks reached 60%, and mortality rates for some flocks were >20%.

Clinical samples from livers, spleens, whole blood, and tumors were collected from chickens in different provinces and sent for laboratory diagnosis. Results showed that the predominant virus in the samples was ALV-J. ...

.. study showed that meat-type birds infected with ALV-J retained a high level of viremia over their lifetime but that layer chickens cleared the infection within a few weeks. Our study demonstrated that ALV-J infection can cause disease in layer chickens and can induce tumors and long-lasting viremia. .. Because ALV-J is vertically transmitted from dam to progeny by the embryo, it represents a potential threat for humans who receive vaccines that are produced in chicken embryonic fibroblasts or embryonated eggs (e.g., yellow fever vaccine and measles and mumps vaccine). An effective vaccine against ALV is not available. Eradication of ALV-J has been difficult because of substantial genetic and antigenic variation among ALV-J isolates as well as high levels of vertical and horizontal transmission.

Virus: Rotaviruses. RNA (EDIM, ADRV, CAL) - gastroenteritis INDEX
https://en.wikipedia.org/wiki/Rotavirus

LINK 02: http://www.cdc.gov/rotavirus/index.html
LINK 03: http://www.zoologix.com/../Datasheets/MouseRotavirus.htm
LINK 04: http://microbewiki.kenyon.edu/index.php/Rotavirus
LINK 05: http://www.mayoclinic.org/../rotavirus/.../CON-20026103
LINK 06: http://www.ncbi.nlm.nih.gov/../PMC2640254/../9866732.pdf
LINK 07: http://www.petmd.com/cat/.../c_ct_rotavirus_infections
LINK 08: http://www.path.org/vaccineresources/rotavirus.php
LINK 09: http://viralzone.expasy.org/all_by_species/107.html
LINK 10: https://en.wikipedia.org/wiki/Rotavirus_vaccine
LINK 11: http://avianmedicine.net/content/uploads/2013/03/32.pdf (2013)

Rotavirus .. is a genus of double-stranded RNA virus in the family Reoviridae.
Rotavirus serotypes were first described in 1980. Nearly every child in the world has been infected with rotavirus at least once by the age of five. Immunity develops with each infection, so subsequent infections are less severe; adults are rarely affected. There are eight species of this virus, referred to as A, B, C, D, E, F, G and H.

Rotavirus A, the most common species, causes more than 90% of rotavirus infections in humans.
... A-E species cause disease in other animals. Within rotavirus A there are different strains, called serotypes. As with influenza virus, a dual classification system is used based on two proteins on the surface of the virus. The glycoprotein VP7 defines the G serotypes and the protease-sensitive protein VP4 defines P serotypes. Because the two genes that determine G-types and P-types can be passed on separately to progeny viruses, different combinations are found.

Rotaviruses are stable in the environment and have been found in estuary samples at levels up to 1-5 infectious particles per US gallon, the viruses survive between 9 and 19 days. Sanitary measures adequate for eliminating bacteria and parasites seem to be ineffective in control of rotavirus, as the incidence of rotavirus infection in countries with high and low health standards is similar.

Avian rotaviruses are thought to be serologically unique from each other and from mammalian rotaviruses. Only chicken and turkey strains have been classified. Some avian group A rotaviruses agglutinate erythrocytes (human type 0 or guinea pig).

Rotaviruses are distributed worldwide and have been documented in chickens, turkeys, Helmeted Guineafowl, pheasants, ducks, pigeons and lovebirds. Avian strains are resistant to ether, chloroform, sodium deoxycholate, pH 3 and 56°C for 30 minutes. The persistence of infectivity in the environment is not known.

The genome of rotavirus consists of 11 unique double helix molecules of RNA which are 18,555 nucleotides in total. Each helix, or segment, is a gene, numbered 1 to 11 by decreasing size. Each gene codes for one protein, except genes 9, which codes for two. The RNA is surrounded by a three-layered icosahedral protein capsid. Viral particles are up to 76.5 nm in diameter and are not enveloped.

At least six of the twelve proteins encoded by the rotavirus genome bind RNA. The role of these proteins play in rotavirus replication is not entirely understood; their functions are thought to be related to RNA synthesis and packaging in the virion, mRNA transport to the site of genome replication, and mRNA translation and regulation of gene expression.

Rotavirus is a cause of enteritis and diarrhea in a variety of mammalian and avian species.
The virus replicates mainly within the enterocytes of the small intestines.
Some strains are known to replicate in the colon and cecum.
Certain strains prefer the duodenum for replication, while others replicate in the upper portion of the jejunum. The virulence of the strains varies (in ducks they are nonvirulent). Because viral replication causes lysis of the host cell, the intestinal absorption in infected birds is dependent on the number of infected enterocytes.

This virus is the leading cause of diarrhea and gastrointestinal upset in cats.
And although it can be seen in cats at any age, kittens are more prone to rotavirus infections. The primary symptom of a rotavirus infection is mild to moderate watery diarrhea. In severe cases, cats may die from dehydration, extreme weight loss, and/or an unwillingness to eat. Because rotaviruses are zoonotic, it is important that pet owners keep infected cats away from young children, infants in particular. When handling the fecal matter of an infected animal, it is especially important to use precautions, such as wearing latex gloves and disinfecting the animal's living area.

Rotavirus A infections can occur throughout life: the first usually produces symptoms, but subsequent infections are typically mild or asymptomatic, as the immune system provides some protection. Consequently, symptomatic infection rates are highest in children under two years of age and decrease progressively towards 45 years of age. Viral diarrhea is highly contagious. The faeces of an infected person can contain more than 10 trillion infectious particles per gram; fewer than 100 of these are required to transmit infection to another person.

Outbreaks of rotavirus A diarrhoea are common among hospitalised infants, young children attending day care centres, and elderly people in nursing homes. An outbreak caused by contaminated municipal water occurred in Colorado in 1981. During 2005, the largest recorded epidemic of diarrhoea occurred in Nicaragua. This unusually large and severe outbreak was associated with mutations in the rotavirus A genome, possibly helping the virus escape the prevalent immunity in the population. A similar large outbreak occurred in Brazil in 1977.

Rotavirus B, also called adult diarrhoea rotavirus or ADRV, has caused major epidemics of severe diarrhoea affecting thousands of people of all ages in China. These epidemics occurred as a result of sewage contamination of drinking water. Rotavirus B infections also occurred in India in 1998; the causative strain was named CAL. Unlike ADRV, the CAL strain is endemic. To date, epidemics caused by rotavirus B have been confined to mainland China, and surveys indicate a lack of immunity to this species in the United States.

Diarrhea in young laboratory mice is often caused by mouse rotavirus, also called epizootic diarrhea of infant mice (EDIM). This RNA virus is highly contagious and is transmitted via contaminated bedding, airborne dust, and through contact with infected mice. The virus is shed in the feces for about 10 days post-infection. Animals are most susceptible between 0 and 14 days of age.

The virus is transmitted by the fecal-oral route.
It infects and damages the cells that line the small intestine and causes gastroenteritis (which is often called "stomach flu" despite having no relation to influenza). Although rotavirus was discovered in 1973 by Ruth Bishop and her colleagues by electron micrograph images and accounts for up to 50% of hospitalisations for severe diarrhoea in infants and children, its importance has been underestimated within the public health community, particularly in developing countries. In addition to its impact on human health, rotavirus also infects animals, and is a pathogen of livestock. There is evidence that animal rotaviruses can infect humans, either by direct transmission of the virus or by contributing one or several RNA segments to reassortants with human strains.

The rotavirus is typically transmitted through contact with contaminated fecal matter.
Cats with underdeveloped or weak immune systems and those living in overly stressed environments are most at risk for the infection. Your veterinarian will try to rule out the following causes for intestinal inflammation before diagnosing rotavirus: feline parvovirus, feline leukemia virus (FeLV), feline coronavirus, feline astrovirus, and feline calicivirus. Other causes for inflammation of the intestine may include fungal infections, parasites, allergies, or exposure to toxins.

Rotaviruses replicate mainly in the gut, and infect enterocytes of the villi of the small intestine, leading to structural and functional changes of the epithelium. The triple protein coats make them resistant to the acidic pH of the stomach and the digestive enzymes in the gut.

The virus enter cells by receptor mediated endocytosis and form a vesicle known as an endosome.
Proteins in the third layer (VP7 and the VP4 spike) disrupt the membrane of the endosome, creating a difference in the calcium concentration. This causes the breakdown of VP7 trimers into single protein subunits, leaving the VP2 and VP6 protein coats around the viral dsRNA, forming a double-layered particle (DLP). The eleven dsRNA strands remain within the protection of the two protein shells and the viral RNA-dependent RNA polymerase creates mRNA transcripts of the double-stranded viral genome. By remaining in the core, the viral RNA evades innate host immune responses called RNA interference that are triggered by the presence of double-stranded RNA.

Rotavirus gastroenteritis is a mild to severe disease characterised by nausea, vomiting, watery diarrhoea, and low-grade fever. Once a child is infected by the virus, there is an incubation period of about two days before symptoms appear. The period of illness is acute. Symptoms often start with vomiting followed by four to eight days of profuse diarrhoea. Dehydration is more common in rotavirus infection than in most of those caused by bacterial pathogens, and is the most common cause of death related to rotavirus infection. Symptoms of dehydration associated with Rotavirus include dizziness while standing, decrease in urination and dry mouth and throat.

During the infection, rotavirus produces mRNA for both protein biosynthesis and gene replication.
Most of the rotavirus proteins accumulate in viroplasm, where the RNA is replicated and the DLPs are assembled. Viroplasm is formed around the cell nucleus as early as two hours after virus infection, and consists of viral factories thought to be made by two viral nonstructural proteins: NSP5 and NSP2. Inhibition of NSP5 by RNA interference results in a sharp decrease in rotavirus replication. The DLPs migrate to the endoplasmic reticulum where they obtain their third, outer layer (formed by VP7 and VP4). The progeny viruses are released from the cell by lysis.

The diarrhoea is caused by multiple activities of the virus.
Malabsorption occurs because of the destruction of gut cells called enterocytes.
The toxic rotavirus protein NSP4 induces age- and calcium ion-dependent chloride secretion, disrupts SGLT1 transporter-mediated reabsorption of water, apparently reduces activity of brush-border membrane disaccharidases, and possibly activates the calcium ion-dependent secretory reflexes of the enteric nervous system. Healthy enterocytes secrete lactase into the small intestine; milk intolerance due to lactase deficiency is a symptom of rotavirus infection, which can persist for weeks. A recurrence of mild diarrhoea often follows the reintroduction of milk into the child's diet, due to bacterial fermentation of the disaccharide lactose in the gut.

Infected mice, usually under 14 days of age, will develop symptoms such as watery and mustard-colored stools, lethargy, and distended abdomens. Rectal impaction may occur at 12 to 16 days of age. If the impacted fecal material is not removed spontaneously or deliberately, the animals will die.

Depending on the severity of diarrhoea, treatment consists of oral rehydration, during which the child is given extra water to drink that contains small amounts of salt and sugar. In 2004, the WHO and UNICEF recommended the use of low-osmolarity oral rehydration solution and zinc supplementation as a two-pronged treatment of acute diarrhoea.

This virus can alter host physiology in multiple ways and can significantly complicate the interpretation of research findings. Examples of such alterations include increased susceptibility to the pathologic effects of copathogens, altered results of dietary and nutritional studies and alterations in gastrointestinal physiology.

Diagnosis based on serology (e.g. ELISA (or enzyme-linked immunosorbent assay)) is inadequate in a number of cases, such as in acute outbreaks when affected mice may not develop ELISA-detectable antibodies for several days after initial exposure, resulting in rapid, undetected spread of the virus through a colony. Direct detection of viral RNA by reverse transcription PCR is useful in such cases.

Vaccination.
Because improved sanitation does not decrease the prevalence of rotaviral disease, and the rate of hospitalizations remains high despite the use of oral rehydrating medicines, the primary public health intervention is vaccination. Two vaccines against Rotavirus A infection are safe and effective in children: Rotarix by GlaxoSmithKline and RotaTeq by Merck. Both are taken orally and contain attenuated live virus. In 2009, the World Health Organization (WHO) recommended that rotavirus vaccine be included in all national immunisation programmes.

In Mexico, which in 2006 was among the first countries in the world to introduce rotavirus vaccine, diarrhoeal disease death rates dropped during the 2009 rotavirus season by more than 65 percent among children age two and under. In Nicaragua, which in 2006 became the first developing country to introduce a rotavirus vaccine, severe rotavirus infections were reduced by 40 percent and emergency room visits by a half. In the United States, rotavirus vaccination since 2006 has led to drops in rotavirus-related hospitalizations by as much as 86 percent. The vaccines may also have prevented illness in non-vaccinated children by limiting the number of circulating infections.

Birds that overcome infections develop intestinal immunity via IgA and humoral antibodies (IgG), which are also transferred via egg yolk to the chick. Humoral antibodies do not protect against infection, even in the newly hatched chick. Cell-mediated immunity is necessary for full protection.

Virus: Lymphocytic choriomeningitis. RNA (LCMV) INDEX
https://en.wikipedia.org/wiki/Lymphocytic_choriomeningitis (2015-09)
a.k.a. Benign lymphocytic meningitis, Lymphocytic meningoencephalitis,
----- Serous lymphocytic meningitis, La Maladie d'Armstrong

LINK 02: http://www.cdc.gov/vhf/lcm/ (2014-05-14)
LINK 03: http://www.zoologix.com/../LymphocyticChoriomeningitis.htm
LINK 04: http://www.cdc.gov/vhf/lcm/pdf/LCM-FactSheet.pdf
LINK 05: http://www.cfsph.iastate.edu/...choriomeningitis.pdf (2010-03)
LINK 06: ..//www.criver.com/...lymphocytic_choriomeningitis_virus.aspx (2009)
LINK 07: https://mothertobaby.org/...choriomeningitis-virus-lcmv-pregnancy/..
LINK 08: http://www.ncbi.nlm.nih.gov/.../09-1347_finalD.pdf (2009)
LINK 09: http://www.ncbi.nlm.nih.gov/.../nihms393928.pdf (2012-09)
LINK 10: http://www.phac-aspc.gc.ca/.../lymp-cho-eng.php (2011)

LCMV is a spherical enveloped arenavirus ... round, oval, or pleomorphic virion, ... with a bipartite single-stranded RNA genome. The virion interior contains granules resembling grains of sand, which are characteristic of the family Arenaviridae, while the surface has hollow golf-club shaped projections.

The lymphocytic choriomeningitis virus is a member of the genus Arenavirus and family Arenaviridae.
There are many strains of this virus with varying pathogenicity. LCMV is classified in the Lassa-Lymphocytic choriomeningitis (Old World) serocomplex of arenaviruses. Two recently discovered viruses in this complex might be able to cause similar illnesses. Kodoko virus, which was detected in Mus Nannomys minutoides (pygmy mice) in Guinea, West Africa, is closely related to LCMV. Its potential to cause disease in humans is unknown. Dandenong virus was isolated from Australian transplant patients who developed a fatal, febrile illness with encephalitis. The virus was transmitted in organs from a donor who had recently returned from a trip to the former Yugoslavia.

Bleach (sodium hypochlorite) or other common household disinfectants will inactivate LCMV. LCMV is susceptible to most detergents and disinfectants including 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde and formaldehyde. The effectiveness of infection quickly declines below pH 5.5 and above pH 8.5. In addition, LCMV can also be inactivated by heat, ultraviolet light or gamma irradiation.

Lymphocytic choriomeningitis virus (LCMV) is a prevalent human pathogen that infects large numbers of people. Despite the fact that it can cause substantial neurological problems, including meningitis, encephalitis, and neurologic birth defects, neurologists are often unfamiliar with it. Perhaps there is no other pathogen about which the gap is wider between what most neurologists should know and what they do know. (2012)

Lymphocytic choriomeningitis (LCM), is a rodent-borne viral infectious disease that presents as aseptic meningitis, encephalitis or meningoencephalitis. Its causative agent is the Lymphocytic Choriomeningitis Virus (LCMV), a member of the family Arenaviridae. The name was coined by Charles Armstrong in 1934.

In mice more than a few days old, LCMV is recognized as foreign.
Some infected mice remain asymptomatic and clear the virus.
Others become acutely ill; the clinical signs may include blepharitis, weakness, convulsions, tremors, photophobia, growth retardation and a rough hair coat. Mice with acute disease either die within a few days to weeks or recover completely. These mice do not become chronically infected. In some strains of mice, LCMV infection is associated with an increased incidence of lymphoma. Generalized immunosuppression can also occur.

LCMV has been isolated from fleas, ticks, cockroaches and Culicoides and Aedes mosquitoes.
Ticks, lice and mosquitoes have been shown to transmit this virus mechanically in the laboratory.
If arthropod-mediated spread occurs in nature, it is thought to play only a minor role in the epidemiology of this disease.

When LCMV attacks a cell, the process of replication starts by attachment of the virus to host receptors through its surface glycoproteins. It is then endocytosed into a vesicle inside the host cell and creates a fusion of the virus and vesicle membranes. The ribonucleocapsid is then released in the cytoplasm. The RNA-dependent, RNA-polymerase brought along with the virus initially binds to a promoter on the L and S segments and begins transcription from negative-stranded to a positive-stranded mRNA. The formation of a strong hairpin sequence at the end of each gene terminates transcription. The mRNA strands are capped by the RNA-dependent, RNA-polymerase in the cytoplasm and are then subsequently translated into the four proteins essential for LCMV assembly. The ribonucleocapsid interacts with the Z matrix protein and buds on the cell membrane, releasing the virion out from the infected cell.

Treatment is symptomatic and supportive. ... anti-inflammatory drugs may also be considered.
Lymphocytic choriomeningitis is not a commonly reported infection in humans, though most infections are mild and are often never diagnosed. Serological surveys suggest that approximately 1-5% of the population in the U.S. and Europe has antibodies to LCMV.

LCMV is naturally spread by the common house mouse, Mus musculus.
Once infected, these mice can become chronically infected by maintaining virus in their blood and/or persistently shedding virus in their urine. Chronically infected female mice usually transmit infection to their offspring (vertical transmission), which in turn become chronically infected. Other modes of mouse-to-mouse transmission include nasal secretions, milk from infected dams, bites, and during social grooming within mouse communities. Airborne transmission also occurs.

Although the house mouse (Mus musculus) is the primary reservoir host for LCMV, it is also often found in the wood mouse (Apodemus sylvaticus) and the yellow-necked mouse (Apodemus flavicollis). Hamster populations can act as reservoir hosts. Other rodents including guinea pigs, rats and chinchillas can be infected but do not appear to maintain the virus. LCMV has been shown to cause illness in New World primates such as macaques, marmosets and tamarins. Infections have also been reported in rabbits, dogs and pigs.

The virus seems to be relatively resistant to drying and therefore humans can become infected by inhaling infectious aerosolized particles of rodent urine, feces, or saliva, by ingesting food contaminated with virus, by contamination of mucous membranes with infected body fluids, or by directly exposing cuts or other open wounds to virus-infected blood. The only documented cases of transmission from animals have occurred between humans and mice or hamsters.

Infected rodents shed the virus in their nasal secretions, saliva, milk, semen, urine, and feces. Physical contact through broken skin, eyes or nose or accidental ingestion of these rodent body fluids may cause an LCMV infection. Sweeping rodent droppings may cause the virus to become airborne and increase the chances of getting an infection. The virus can also be passed through rodent bites. Human infection with this virus is more common in the fall when rodents move indoors into homes. Passing the LCMV infection from person to person has not been seen except in the case of mother to baby during pregnancy or delivery.

Cases of lymphocytic choriomeningitis have been reported in North and South America, Europe, Australia, and Japan, particularly during the 1900s. However, infection may occur wherever an infected rodent host population exists. LCMV occurs worldwide and its natural host, the rodent, has become established on all continents, except Antarctica.

Seroprevalence is approximately 5% (0.7-4.7%) of the US population.
It tends to be more common among lower socio-economic groupings, probably reflecting more frequent and direct contacts with mice. However, obtaining an accurate sense of prevalence by geographic region is difficult due to underreporting.

In cases of acquired infection, the virus typically enters the human in an aerosolized form and is deposited in the lung, where initial viral replication occurs. This parenchymal lung infection often manifests as interstitial lung infiltrates and lung edema early in the course of disease. The virus then enters the blood stream and travels to other organs, where further viral replication occurs. Ultimately, LCMV reaches the meninges, choroid plexus, and ventricular ependymal linings, where the virus replicates to high titers and where the inflammatory response produces the characteristic pathology and symptoms of meningitis that give the virus its name.

In acquired LCMV infection, the host immune response is both protective and deleterious.
The immune response is protective in the sense that it performs the critically important function of eliminating the virus and protecting against repeat infection. However, the immune response is deleterious in the sense that tissue inflammation underlies the symptoms of disease.

The disease is likely underdiagnosed because only a limited number of commercial laboratories offer LCMV testing. Diagnosed cases of LCMV are often identified because they are part of a larger outbreak. ... Health departments should consider making LCMV a reportable condition, and, if aseptic meningitis is reportable, questions should be added to case investigation forms regarding rodent exposure. LCMV was made reportable in New York City in 2009. Only with a better understanding of the true incidence of LCMV will authorities be able to enact measures to better prevent and control this disease in the vulnerable sections of our society.

Symptoms.
LCMV is a virus that can cause flu-like symptoms including fever, muscle aches, fatigue, nausea and vomiting. Some people will develop meningitis (inflammation of the spinal cord) or encephalitis (inflammation of the brain) or both. Some people will not have any symptoms at all. The onset of flu-like symptoms starts 1-2 weeks after being exposed to the virus. These symptoms can last as long as a week. If the infection goes on to affect the spinal cord or brain, the entire length of infection can be up to 3 weeks.

You may have no symptoms and still have LCMV infection.
However, you may have some of the following: mild fever, fatigue, lack of appetite, muscle aches, headache, nausea, and vomiting. After a few days of recovery, you may have symptoms of meningitis such as fever, headache and a stiff neck, or symptoms of encephalitis such drowsiness, confusion, sensory disturbances, and/or motor problems, such as paralysis).

Onset typically occurs between one or two weeks after exposure to the virus and is followed by a biphasic febrile illness. During the initial or prodromal phase, which may last up to a week, common symptoms include fever, lack of appetite, headache, muscle aches, malaise, nausea, and/or vomiting. Less frequent symptoms include a sore throat and cough, as well as joint, chest, and parotid pain.

The onset of the second phase occurs several days after recovery, and consists of symptoms of meningitis or encephalitis. Pathological findings during the first stage consist of leukopenia and thrombocytopenia. During the second phase, typical findings include elevated protein levels, increased leukocyte count, or a decrease in glucose levels of the cerebrospinal fluid).

Infections in persons with an intact immune system are often asymptomatic or result in a mild self-limiting illness including fever, chills, myalgia, and headache. Photophobia, anorexia, testicular or parotid pain, pharyngitis, and cough have also been noted. Leukopenia, thrombocytopenia, and mild liver function abnormalities are common and may last 1-3 weeks.

Central nervous system invasion is seen only in a few patients either after an initial febrile illness or, less commonly without any early symptoms. During this neurologic phase, most patients have aseptic meningitis and a peripheral leukocytosis. Cerebrospinal fluid (CSF) leukocyte cell counts often exceed 1,000/uL, and glucose levels are low. Infection is rarely fatal, although ascending paralysis, transverse myelitis, or encephalitis may develop.

Occasionally, a patient improves for a few days, then relapses with aseptic meningitis, or very rarely, meningoencephalitis. Patients with meningitis may have a stiff neck, fever, headache, myalgia, nausea and malaise. In some occasions, meningitis occurs without a prodromal syndrome. Meningoencephalitis is characterized by more profound neurological signs such as confusion, drowsiness, sensory abnormalities and motor signs.

Under reported complications include myelitis, Guillain-Barre-type syndrome, cranial nerve palsies, transient or permanent hydrocephalus (fluid in the brain), sensorineural hearing loss, orchitis, arthritis and parotitis. LCMV infections have also been associated with pancreatitis, pneumonitis, myocarditis and pericarditis. The entire illness usually lasts 1 to 3 weeks, nonetheless, temporary or permanent neurological damage is possible in all central nervous system infections, especially in cases of meningoencephalitis. Chronic infections have not been reported in humans and deaths rarely occur.

Congenital infection
Lymphocytic choriomeningitis is a particular concern in obstetrics, as vertical transmission is known to occur. ... the virus has damaging effects upon the fetus. If infection occurs during the first trimester, LCMV results in an increased risk of spontaneous abortion. Later congenital infection may lead to malformations such as intracranial calcifications, hydrocephalus (fluid in the brain), microcephaly or macrocephaly, intellectual disabilities, and seizures. Other findings include chorioretinitis (eye problems which can lead to vision loss), and optic atrophy. Mortality among infants is approximately 30%. Among the survivors, two thirds have lasting neurologic abnormalities.

Other ocular defects including optic atrophy, microphthalmia, vitreitis, leukokoria and cataracts can also be seen. Most of the infants in one case series were of normal birth weight, although 30% were underweight. Aspiration pneumonia can be a fatal complication. Infants who survive may have severe neurological defects including epilepsy, impaired coordination, visual loss or blindness, spastic diplegia or quadriparesis/quadriplegia, delayed development and intellectual disability. Less severe cases with isolated cerebellar hypoplasia and symptoms of ataxia and jitteriness have been reported occasionally. There have also been rare cases with evidence of chorioretinitis (eye problems which can lead to vision loss) but without neurological signs. Systemic signs seem to be rare, but hepatosplenomegaly, thrombocytopenia and hyperbilirubinemia have been documented in a few cases, and skin blisters were reported in one infant.

While the vision losses in congenital LCMV infection are often severe, it is the effect of the virus on the developing brain that causes the greatest disability. Congenital LCMV infection often leads to macrocephaly or to microcephaly. The cases of macrocephaly are almost invariably due to noncommunicating hydrocephalus, reflecting inflammation and blockade of the ventricular system at the cerebral aqueduct. Microcephaly in the setting of congenital LCMV infection is due to a virus-induced failure of brain growth and to immune-mediated destruction of infected brain tissue. Additional pathologic features often observed include periventricular calcifications, cortical dysplasia, focal cerebral destruction, and cerebellar hypoplasia1.

Brain function in children with congenital LCMV infection is virtually always adversely affected. However, the impairments and severity vary from case to case. Children with microencephaly and periventricular calcifications virtually always have severe mental retardation, spastic quadriparesis, and epilepsy. In contrast, patients with isolated cerebellar hypoplasia typically have ataxia and mild-to-moderate learning disabilities.

If a woman has come into contact with a rodent during pregnancy and LCM symptoms are manifested, a blood test is available to determine previous or current infection. A history of infection does not pose a risk for future pregnancies.

Patients infected in solid organ transplants have developed a severe fatal illness, starting within weeks of the transplant. In all reported cases, the initial symptoms included fever, lethargy, anorexia and leukopenia, and quickly progressed to multisystem organ failure, hepatic insufficiency or severe hepatitis, dysfunction of the transplanted organ, coagulopathy, hypoxia, multiple bacteremias and shock. Localized rash and diarrhea were also seen in some patients. Nearly all cases have been fatal.

Pathological diagnosis of congenital infection is performed using either an immunofluorescent antibody (IFA) test or an enzyme immunoassay to detect specific antibody in blood or cerebrospinal fluid. A PCR assay has been recently developed which may be used in the future for prenatal diagnosis; however, the virus is not always present in the blood or CSF when the affected child is born. Diagnoses is subject to methodological shortcomings in regard to specificity and sensitivity of assays used. For this reason, LCMV may be more common than is realized.

We recommend enzyme immunoassay-based testing of CSF and serum when LCMV is considered.
Public health surveillance, rodent control, healthcare provider education, and improved laboratory testing can enhance recognition of illness. LCMV is not known to induce persistent infection in humans, and the time course of viral clearance from an infected human fetus is unknown. A fetus may sustain substantial brain damage from LCMV but effectively clear the virus and have no LCMV RNA to be detected by PCR in the postnatal period.

Certain findings on ultrasound, such as enlarged areas of the brain (ventriculomegaly), excess fluid in the skull or bleeding around the brain (hydrocephaly, intracranial hemorrhage), or buildup of fluid in the body tissues (hydrops), can indicate a possible LCMV infection. The mother's blood can also be tested for an LCMV infection.

Another detection assay is the reverse transcription polymerase chain reaction (RT-PCR) tests which may detect nucleic acids in the blood and cerebrospinal fluid.(CSF) Virus isolation is not used for diagnosis in most cases but it can be isolated from the blood or nasopharyngeal fluid early in the course of the disease, or from CSF in patients with meningitis.

LCMV causes callitrichid hepatitis in New World primates.
The initial signs are nonspecific and may include fever, anorexia, dyspnea, weakness and lethargy.
Jaundice is characteristic and petechial hemorrhages may develop. These signs are often followed by prostration and death.

Serologic testing is not recommended for pet rodents, as it has been unreliable in detecting antibodies in animals with active infections.

LCM is known as the prototype arenavirus, and has been instrumental in our understanding of the major pathogenetic mechanisms of all arenaviruses. ... An important aspect of the present modern society is the thorough understanding of the burden of cancer. In many ways, this disease mirrors persistent viral infection, in the way that it evades and progresses despite the immune system's effort to eliminate it. ... LCMV is a prototype of more severe hemorrhagic fever viruses, especially Lassa virus with the greatest prevalence in sub-Saharan Africa. However, other strains of this virus (Junin and Machupo viruses) are present in parts of South America and other strains continue to significantly affect the southern African population. Since the modern society continue to become a more inter-connected world, the spread of these virus strains will continue to pose a severe threat around the globe.

While acquired LCMV infection is usually mild and self-limited, it is sometimes much more severe, and fatalities from acquired LCMV infection have been reported. The clinical spectrum of acquired LCMV infection is broad. In as many as one third of infected people, the disease is asymptomatic. On the other hand, some patients develop not only CNS symptoms, but extraneural disease, as well. Pneumonitis, myocarditis, orchitis, parotitis, dermatitis, and pharyngitis have all complicated LCMV infections. In addition, the CNS disease in some patients may be considerably more severe than just aseptic meningitis. Other CNS effects have included encephalitis, hydrocephalus, transverse myelitis, and Guillain-Barre syndrome.

The principal differential diagnoses of congenital LCMV infection are the other infectious pathogens that can cross the placenta and damage the developing fetus. These infectious pathogens are linked conceptually by the acronym "TORCHS" and include Toxoplasma gondii, rubella virus, cytomegalovirus, herpes simplex virus, and syphilis. Congential varicella virus, parechovirus, and human immunodeficiency virus (HIV) could also masquerade as LCMV.

Cytomegalovirus and toxoplasmosis may be particularly difficult to differentiate from LCMV, because all three of these infections can produce microencephaly, intracranial calcifications, and chorioretinitis. Although clinical clues may aid in distinguishing one congenital infection from another, definitive identification of the causative infectious agent usually requires laboratory testing, including cultures and serologic studies.

The differential diagnosis of congenital LCMV infection also includes several noninfectious entities. Chromosomal abnormalities are prominent causes of microencephaly. However, abnormalities in the structure or number of chromosomes commonly induce dysmorphic features (especially of the hands, feet, and facies) or structural abnormalities (especially of the heart or genitourinary system) that are not observed in congenital LCMV infection. Several genetic disorders can mimic congenital LCMV infection. In particular, Aicardi-Goutieres syndrome is an autosomal recessive disorder that often presents as neonatal encephalopathy and intracranial calcifications38. However, its progressive course and identifiable mutations in the TREX1 and RNASEH2 genes distinguish it from congenital LCMV infection.

A second disorder that mimics congenital LCMV and that may be genetic in etiology is pseudo-TORCH syndrome. In this disorder, infants have many of the classic features of the common congenital infections that gave rise to the TORCH acronym (toxoplasmosis, rubella, cytomegalovirus, and herpes viruses). However, in pseudo-TORCH syndrome, no serological or microbiologic evidence of a congenital infection is ever identified. Because multiple siblings may be similarly affected, pseudo-TORCH syndrome is presumed to be a genetic disorder. However, no genetic locus for pseudo-TORCH syndrome has been identified. The possibility exists that pseudo-TORCH syndrome is actually an unidentified congenital infection.

Congenital LCMV infection can be distinguished from pseudo-TORCH syndrome in several ways.
First, most mothers of infants with congenital LCMV infection have a history of exposure to wild mice and experienced a definite "flu-like" illness during the pregnancy; these historical factors are typically absent in pseudo-TORCH syndrome. Most importantly, chorioretinitis is present in all cases of congenital LCMV infection and absent in all cases of pseudo-TORCH syndrome.

LABORATORY-ACQUIRED INFECTIONS:
LCMV infection is a well known occupational risk for those working with rodents, especially hamsters and mice. 76 cases were reported up until 1978, including 3 outbreaks between 1973 and 1975 among laboratory workers who had handled hamsters that had tumour grafts containing LCMV. Further cases have occurred since then, notably in an outbreak associated with nude mice, in which 9% of 82 animal care workers were found to be seropositive for LCMV.

CONTAINMENT REQUIREMENTS:
Containment Level 3 facilities, equipment, and operational practices for work involving infectious or potentially infectious materials, animals, or cultures. These containment levels apply to the species as a whole, and may not be representative of all strains and clonal isolates.

PROTECTIVE CLOTHING:
Personnel entering the laboratory should remove street clothing and jewellery, and change into dedicated laboratory clothing and shoes, or don full coverage protective clothing (i.e., completely covering all street clothing). Additional protection may be worn over laboratory clothing when infectious materials are directly handled, such as solid-front gowns with tight fitting wrists, gloves, and respiratory protection. Eye protection must be used where there is a known or potential risk of exposure to splashes.

OTHER PRECAUTIONS:
All activities with infectious material should be conducted in a biological safety cabinet (BSC) or other appropriate primary containment device in combination with personal protective equipment. Centrifugation of infected materials must be carried out in closed containers placed in sealed safety cups, or in rotors that are loaded or unloaded in a biological safety cabinet. The use of needles, syringes, and other sharp objects should be strictly limited. Open wounds, cuts, scratches, and grazes should be covered with waterproof dressings. Additional precautions should be considered with work involving animals or large scale activities.

Virus: Theiler's encephalomyelitis. RNA (TMEV, GD VII, DA/TO, SAFV, VHEV) INDEX
https://en.wikipedia.org/../Theiler%27s_encephalomyelitis_virus (2015-03-14)

LINK 02: https://www.ncbi.nlm.nih.gov/../PMC2133518/../705.pdf
LINK 03: http://cat.inist.fr/?aModele=afficheN&cpsidt=1537965
LINK 04: http://www.zoologix.com/rodent/Datasheets/Theilers.htm
LINK 05: http://dora.missouri.edu/../mouse-encephalomyelitis.. (2013)
LINK 06: http://www.criver.com/.../rm_ld_r_theiloviruses.aspx (2009)
LINK 07: http://viralzone.expasy.org/all_by_species/99.html (2008)
LINK 08: http://link.springer.com/article/10.1080/... (2007-01)
LINK 09: http://www.viprbrc.org/../viprStrainDetails... (2015-09-10)
LINK 10: http://www.uic.edu/labs/lipton/pubs/8909.pdf (2004)
LINK 11: http://tigger.uic.edu/.../virol2001.pdf (2001)
LINK 12: http://www.viprbrc.org/...picorna (2015-09-10)
LINK 13: http://www.ncbi.nlm.nih.gov/../PMC112673/ (1999)
LINK 14: http://www.pnas.org/.../4125.full.pdf (1990)

PLoS Pathogens -- www.plospathogens.org -- May 2009 -- Volume 5 -- Issue 5 -- e1000416

Theiler's murine encephalomyelitis virus (TMEV) belongs to the genus Cardiovirus of the family Picornaviridae and is divided into two subgroups strains on the basis of their different biological activities. Theiler's murine encephalomyelitis virus (TMEV) is a single-stranded RNA picornavirus that persistently infects the murine central nervous system. ... Mice are the natural host of this virus. In the wild it produces a gastrointestinal infection that may be complicated by concomitant infection of the nervous system. The virion RNA is infectious and serves as both the genome and viral messenger RNA.

GDVII subgroup strains are highly virulent and produce acute fatal polioencephalomyelitis in mice.
In the few surviving mice, neither viral persistence nor demyelination occurs.
... the defense mechanism against Theiler's virus strain GD VII is dependent on Mac-1+ (macrophage antigen-1) cells in the spinal cord. It is possible that the rapid death of the neuron does not give the virus time to be transported down the axon. In contrast, the persisting DA strain exhibits a much more attenuated phenotype in neurons, which may allow the virus to reach the white matter by axonal transport.

There are two main groups of TMEV.
One includes the GDVII and FA viruses, which produce an acute fulminant encephalomyelitis, which is fatal in about a week. The other, called Theiler's original group, includes the DA, BeAn, and WW viruses. These produce a chronic persistent central nervous system infection, accompanied by inflammatory demyelinating lesions of the spinal cord with features very similar to those of demyelinating plaques seen in human multiple sclerosis. The demyelination induced by TMEV infection is mediated by the immune system rather than as a consequence of viral infection of oligodendrocytes, the myelin forming cells. DA strain persists in the spinal cords of mice despite a vigorous humoral immune response.

Members of both neurovirulence groups are 90% identical in nucleotide sequences, 95% identical in amino acid contents, and differ only slightly in their overall three-dimensional structures. Despite their close genetic and structural relatedness, these viruses differ significantly in their mode of binding to mammalian cells and in their association with intracellular membranes during replication. ... the DA strain of Theiler's virus sequentially infects neurons in the gray matter and glial cells in the white matter of the spinal cord. It persists in the latter throughout the life of the animal. Several observations suggest that the virus spreads from the gray to the white matter by axonal transport. In contrast, the neurovirulent GDVII strain causes a fatal encephalitis with lytic infection of neurons. It does not infect the white matter of the spinal cord efficiently and does not persist in survivors.

The family Picornaviridae contains well-known human pathogens (e.g., poliovirus, coxsackievirus, rhinovirus, and parechovirus). In addition, this family contains a number of viruses that infect animals, including members of the genus Cardiovirus such as Encephalomyocarditis virus (EMCV) and Theiler's murine encephalomyelits virus (TMEV). The latter are important murine pathogens that cause myocarditis, type 1 diabetes and chronic inflammation in the brains, mimicking multiple sclerosis. Recently, a new picornavirus was isolated from humans, named Saffold virus (SAFV). The virus is genetically related to Theiler's virus and classified as a new species in the genus Cardiovirus, which until the discovery of SAFV did not contain human viruses.

The family Picornaviridae is one of the largest RNA virus families, containing 8 established and 6 proposed genera and at almost 33 species. Four genera contain clinically important viruses infecting humans, i.e. Enterovirus (which since recently also includes the human rhinoviruses), Parechovirus, Hepatovirus, and Kobuvirus. This family also contains economically important animal pathogens such as Foot-and-mouth-disease virus, a species belonging to the Aphthovirus genus. Other well-known animal pathogens are Theilovirus and Encephalomyocarditis virus (EMCV), two species that belong to the Cardiovirus genus and are associated with disease in rodents and swine.

The Theilovirus species is represented by Theiler's murine encephalomyelitis virus (TMEV) and rat encephalomyelitis virus (also called Theiler's rat virus, TRV). TMEV is an enteric pathogen that primarily causes asymptomatic infections of the alimentary tract. However, extra-intestinal infection can occur and produce acute fatal encephalomyelitis or a chronic demyelinating disease relevant for multiple sclerosis, depending on the TMEV strain involved. TMEV can furthermore cause serious foetal pathology and placental damage, depending on the gestational phase of infection.

The question of whether authentic human cardioviruses exist has remained unclear for a long time.
A Theiler's-like cardiovirus, named Vilyuisk human encephalomyelitis virus (VHEV), has been implicated in an outbreak of a neurodegenerative disease among the Yakuts people in Vilyuisk, Siberia, in the 1950s. However, this virus, which was isolated upon multiple passages in mice and cell cultures, shows close relationship with TRV and TMEV, raising the possibility that it represents a contaminating animal cardiovirus. Recently, however, strong evidence has been obtained for the existence of human cardioviruses.

In 2007, the genomic sequence was reported of a cardiovirus, provisionally named Saffold virus (SAFV), amplified in cell culture from the stool of an infant presenting with fever of unknown origin in 1981. Following this discovery, SAFVs were detected by molecular techniques in nasopharyngeal aspirates of 3 children with respiratory symptoms in Canada, in stool samples from 6 paediatric patients suffering from gastroenteritis from Germany and Brazil, and in 1 respiratory secretion from a patient presenting with an influenza-like illness and 6 stool specimens from patients in a gastroenteritis cohort in California.

Recently, (2009) SAFVs were detected in stool samples from 6 South Asian children with non-polio acute flaccid paralysis (AFP), but also in stool samples from 5 children without overt neurological symptoms. All SAFVs identified to date are significantly divergent from the documented animal cardioviruses, especially in the region encoding the structural capsid proteins that are important for receptor binding. Phylogenetic analysis suggests the existence of 8 distinct genetic SAFV lineages. Together, these findings suggest that SAFVs are genuine human viruses that can be sporadically found in fecal and respiratory specimens of children, with or without symptomatology, but that until recently have gone largely undetected most likely because of their fastidious growth. Thus, their relationship with clinical disease remains to be established.

In December 2007, a virus was isolated from a stool sample obtained from a 13 month-old boy who presented with vomiting. .. the complaints were not due to an infection but to an anatomical mal-position of the jejunum. ... a virus that was acid-stable, chloroform resistant and ... could not be typed as an enterovirus or parechovirus. ... Based on a sequence comparison (BLASTn search), the virus was identified as a SAFV. ... Phylogenetic analysis of the available VP1 coding regions revealed six clades: TMEV, TRV, VHEV, SAFV-1, SAFV-2, and SAFV-3.

... antibodies against SAFV-3 are highly prevalent in the Netherlands and that infection most likely occurs early in life. ... Neutralizing antibodies were found in 77% of Finnish children and 100% of people living in Africa or Indonesia, indicating that infection with SAFV-3 has a wide spread distribution among humans. Moreover, the presence of neutralizing antibodies in samples collected in 1997-1998 proves that this particular virus or a closely related one is circulating for at least 10 years.

TMEV is thought to be an excellent animal model for the human demyelinating disease, multiple sclerosis.
There are several interesting features regarding TMEV persistence.

1) A majority of TMEV-infected cells during the chronic stage of disease contain a relatively small number of copies of the genome (100-500 copies) which is insufficient for the induction of detectable expression of viral proteins. The limited viral protein synthesis is predicted to induce relatively little cytopathic effect, and therefore to allow the virus to bypass immunological clearance.

2) Sequence analysis of escape mutant viruses resistant to DA neutralizing monoclonal antibodies has identified four separate sites for amino acid mutations of capsid proteins that lead to a decrease in demyelinating activity. All of these sites are located on or near the rim of the 'pit', a putative receptor binding region of the virus. These findings suggest that antibody mediates neutralization by preventing the binding of virus to the cell receptor and that demyelination with virus persistence can be interfered with by preventing viral attachment to receptors of particular cell types.

3) Finally, a 17 kDa protein, designated as L*, is only synthesized in DA subgroup strains from an alternative, out-of-frame, initiation site. Studies of a DA mutant virus, which has an ACG rather than AUG at the L* initiation site and therefore does not synthesize L* protein, demonstrated that this protein is important for the virus growth in particular cell types and is critical for DA-induced demyelinating disease and virus persistence.

Many bacteria and viruses infect humans, without pathology in normal individuals.
If certain individuals are genetically predisposed to immunological intolerance of these commensal organisms, pathology can occur. The Saffold virus, a human virus discovered in 2007, has been shown to have high prevalence in humans (>90%). It may be an important link between the study of mouse TMEV-induced encephalomyelitis and human Multiple Sclerosis.

The virus is spread horizontally by contact with feces and urine (dirty bedding).
In experimental infections with GDVII, virus was excreted for up to 154 days, even in the presence of circulating antibody. Most infected mice do not express clinical signs of disease. ... lethargy and loss of body weight. Experimental intracerebral inoculation with GDVII can cause acute encephalitis, while inoculation with DA causes persistent infections and demyelinating disease. Mice with the demyelinating disease exhibit paresis and eventually paralysis.

Most infected mice have no gross or histologic lesions.
The virus can cause transient and acute encephalitis with gliosis and perivascular and meningeal infiltrates. In prolonged infections, an immune-mediated demyelinating disease develops. The leptomeningeal and white matter of the spinal cord are infiltrated with lymphocytes and spongiform lesions occur in white matter of the brain stem and spinal cord.

Virus: Kilham rat parvovirus. DNA (RV, KRV, RPV-1, RPV-2, MKV) INDEX
https://en.wikipedia.org/wiki/Protoparvovirus (2015-08-28)

LINK 02: http://zoologix.com/.../KVirus.htm (2012)
LINK 03: http://www.usbio.net/item/209245
LINK 04: http://www.zoologix.com/.../KVirus.htm (2009)
LINK 05: http://ratguide.com/.../kilham_rat_virus.php (2012-02-17)
LINK 06: http://www.criver.com/../rm_ld_r_rat_parvoviruses.aspx (2009)
LINK 07: http://www.gv-solas.de/../Infektionserreger/KRV.pdf (1996)
LINK 08: http://www.ncbi.nlm.nih.gov/.../jvirol00290-0016.pdf (1970)
LINK 09: ..www.ncbi.nlm.nih.gov/../PMC1143717/../1660-04.pdf (2005)
LINK 10: http://eurekamag.com/.../028670591.php#close (1979)
LINK 11: http://viralzone.expasy.org/../58.html (2010)

KRV is a single-stranded DNA virus, family Parvoviridae, genus Parvovirus.
KRV is the type species of the genus. It is synonymous with rat virus (RV) and parvovirus RPV-1.
Kilham and Olivier (1959) named this virus "Rat Virus (RV)" and that is its official taxonomic name. ... more distinctive name Kilham Rat Virus (KRV), .. is commonly used in the United States. Approximately a dozen strains of the virus have been isolated. The virion is non-enveloped, and measures 18-30 nm in diameter. The genus Parvovirus presently contains 13 distinct serotypes, three of which occur in rodents: KRV, H-1 virus, and Minute Virus of Mice.

Protoparvovirus is a genus of viruses in the subfamily Parvovirinae of the virus family Parvoviridae. Vertebrates serve as natural hosts. There are currently five species in this genus including the type species Rodent protoparvovirus. This genus includes canine parvovirus, which causes gastrointestinal tract damage in puppies that is about 80% fatal. Until 2014, the genus was called Parvovirus, but it was renamed to eliminate confusion between members of this genus and members of the entire family Parvoviridae.

Kilham rat virus (KRV) was discovered by Kilham and Olivier (1959) during attempts to isolate a suspected oncogenic virus from rats with experimental tumors (a Cysticercus fasciolaris-induced sarcoma in F344 rats and a transplantable leukemia in OM rats). ... Parvoviruses are remarkably resistant to environmental conditions.
Infectivity is retained after heating at 80°C for 2 hours or 40°C for up to 60 days.
They also are resistant to dessication, pH 2 to 11, chloroform, ether, and alcohol.
KRV infection has been reported to induce interferon production in vivo.

Mouse K virus (MKV) was first discovered by Lawrence Kilham - thus "K" virus.
It belongs to the family Pavovaviridae. The virus is usually spread by the oronasal route.
When a young mouse is orally inoculated with the virus, the virus first replicates in the intestine and then spreads to other organs such as liver, lung, spleen and brain. Older mice may mount an immune response to the virus and thus may limit the spread of the virus through the body. However, athymic or nude mice suffer significantly if infected. Porcine parvovirus, PPV, one of the major causes of reproductive failure in swine, was isolated from infected pigs. A new virus in this genus was discovered in the feces of children from Burkina Faso, and named using the siglum Bufavirus. Three genotypes of bufaviruses have so far been detected, circulating in Tunisia, Finland and Bhutan.

Because of the potential for transmission across the placenta or in semen, rederived offspring should be strictly quarantined until demonstrated free of the virus. Transmission of the virus can be limited by the use of cages with filter covers, by reduction of staff movements, and by strict measures of housing and care. Parvoviruses can survive in dust and debris found in ventilation systems and these should not be overlooked in cleaning animal housing and experimental areas. Staff who work in the animal houses must not have rodents as pets.

Parvoviruses target replicating tissue and can cause cell and tissue destruction.
This explains why RV, while in its active stage, will interfere with the formation of offspring while they are developing in utero or perinatally. Such interference may result in smaller litters, stillborns, or the resorption of litters.

Antibodies will form within 7-10 days after exposure.
It has been concluded through research that the anti-viral antibodies do not clear infection.
If an exposed female has already built up antibodies they will be passed on to her offspring in colostrum during suckling. After the transference of the antibodies these young rats will test positive, but will not be infected. These babies may then become infected 2-7 months after the effects of maternal antibodies have worn off. At this point they would have less evidence of clinical disease.

If the mother has been infected and has not had time to build up antibodies, then the developing babies can be affected in utero. Infection early in the pregnancy may lead to partial or total resorption of the fetuses. If a dam is infected in the last trimester (with no antibodies present) she may then transfer the virus either in utero or through milk, after they are born, to the surviving offspring. Infection occurring from the third trimester in utero through the first week of life can result in rats with a more persistent infection. Early infection such as this can take up to six months to clear. The persistence of the virus depends largely on the age and/or immunocompetence of the rat when it is exposed. The younger the rat is at initial infection the longer the disease will persist. ..

Once the rats get past the active infection, typically 60-90 days, the virus does remain in certain tissues including the spleen, lymph nodes, and walls of blood vessels. These areas of infection are not affiliated with the transmission routes (such as the urinary tract, mammary glands, and digestive system) and therefore the virus will no longer be transmitted via urine, milk, or feces. Note that once a rat is exposed it will continue to test positive for RV on serology tests even after the active infection as cleared.

Research has shown that if a normally post-infectious rat is stressed either physically or psychologically there is a possibility that the RV can be reactivated and transmitted to other rats. Other factors that contribute to infection and transmission issues are the rat's natural resistance to disease, whether the rat is immunocompromised (e.g. athymic), and the particular strain of RV you are dealing with. In a rat with immune system disorders it would be possible for RV to persistently infect.

In naturally infected colonies of mice, significant clinical symptoms are usually absent and these infected mice may become carriers of the virus and pass it to young mice. Infection with rat parvoviruses may cause rare clinical illness in animals, may affect the immune system, resulting in lower tumor take, alteration of immune responses, and induction of cytokine production, and may induce hepatocellular necrosis in animals exposed to other hepatic insults. Infection with parvoviruses may affect studies involving fetal development.

Like mouse parvoviruses, rat parvoviruses, RPV (formerly rat orphan parvovirus) -- especially H-1, are oncotropic and oncolytic and are being explored as potential anti-cancer agents. Infection of animals with RV during development has the potential to negatively affect a variety of body systems, including the nervous, lymphatic, gastrointestinal, hematopoietic, and reproductive.

KRV has been reported to suppress the development of leukemia due to Moloney virus.

There are few reports of natural disease or interference with research due to this virus, but its high prevalence in rats and propensity for damaging populations of replicating cells in vivo and in vitro make it a significant pathogen.

Transmission of KRV is primarily by the horizontal route, either through direct contact or fomites. Contaminated fomites are probably important because parvoviruses are extremely stable to dessication. The efficiency of horizontal transmission may depend on strain of virus and age at which rats are infected. Virus has been reported to be shed in urine, feces, milk, and nasal secretions. Rats infected by the oronasal route at two days of age transmitted the virus to cagemates for 10 weeks, whereas rats infected at 4 weeks of age were able to infect their cagemates for only 3 weeks post infection. .. Persistent infection has been shown to occur for up to 14 weeks in rats infected as infants.

Natural disease due to KRV was observed in 13-day pregnant rats by Kilham and Margolis (1966).
They reported increased numbers of uterine resorption sites in the dams and runting, ataxia, cerebellar hypoplasia, and jaundice in pups from several litters. KRV was isolated from the pups, as well as from tissues, feces, and milk of the dams.

Spontaneous deaths, scrotal cyanosis, abdominal swelling, dehydration, and other signs of severe illness occurred in juvenile and 7-week-old male rats within 2 weeks after these animals were added to a colony of adult rats that were serologically positive for KRV.

KRV infects actively replicating (S-phase) cells and thus, has a predilection for proliferating and growing tissues. Also, productive infection is always lytic and thus, infection usually leads to cell destruction. For these reasons, the major pathologic effects of KRV infection would be expected to occur during fetal development and early life. ... Natural infections of KRV also have been the cause of severe disease in rats from birth to 9 weeks of age ... stunting, cerebellar hypoplasia, jaundice, and hemorrhagic infarction with thrombosis in multiple organs (including brain, spinal cord, testes, and epididymis). Amphophilic intranuclear inclusions occurred in the endothelium and other cells of affected organs. Focal necrosis, hypertrophy and vacuolar degeneration of hepatocytes, cholangitis, and biliary hyperplasia can occur in the liver.

During the active stage of the infection clinical signs may include:

    Small litters
    Infertility
    Runting
    Stillborn babies
    Litter resorption 

On rare occasions RV can become clinically evident in unnaturally infected rats.
If this occurs the rat may experience failure to thrive, ataxia (uncoordinated muscle movements), cerebellar hypoplasia (congenital damage to the part of the brain that controls coordination of movement), or jaundice (yellowing of the skin & mucus membranes due to the liver's inability to process bile). These signs have been seen in rats experimentally exposed to virulent strains of RV during the late stage of pregnancy or the first week of life. Scrotal cyanosis has also been seen in rats experimentally infected with RV.

Attempting to Clear a Colony of RV
Some breeders and fanciers may choose to attempt to clear their colonies of RV.
It may be possible to do so although there are factors that make such an attempt difficult.
The effort would mean that the fancier would have to consider not only the rats, but also the environmental aspects. Even with the strictest procedures there are no guarantees.

Parvoviruses are extremely stable in the environment and can remain viable for weeks or months.
It is this characteristic that facilitated the worldwide spread of canine parvovirus in the early 1980s. Removing the virus from an environment, especially in a non-lab setting, would be a monumental. The first step would be to thoroughly scrub to remove all debris on cages, accessories, walls, and floors with soapy water then sterilize with bleach solution. No surface, crack, corner, or wire could be ignored if the clearance is to be as complete as possible. Carpet, furniture, and drapes may present a problem during an attempt to disinfect. Dishes, bowls, and water bottles would also need this treatment. Porous items such as wicker nests and wood accessories could potentially harbor the virus and elimination may need to be considered. Food and litter, even though unused may also have been contaminated during normal handling and may also need to be eliminated. This would have to be completed after the quarantine and well before any rats were brought in. ..

Diagnosis of mice infected with K virus is sometimes done by serology testing.
However, since many mice may have had prior exposure to this virus, a positive serology result may not indicate current carrier status. Molecular detection by PCR can provide rapid, highly sensitive, highly specific identification of the presence of the virus.

Virus: Newcastle disease. RNA (NDV) INDEX
https://en.wikipedia.org/wiki/Newcastle_disease (2015-07-14)

LINK 2: http://www.avianbiotech.com/Diseases/Newcastle.htm (2009)
LINK 3: http://www.brandeis.edu/wanghlab/../newcastle.html
LINK 4: http://beautyofbirds.com/newcastledisease.html (2011)
LINK 5: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3550779/
LINK 6: http://www.phsource.us/../PDA/VELOGENIC%20NEWCASTLE%20DISEASE.pdf
LINK 7: ..//www.jove.com/...-newcastle-disease-virus... (2013-11-10)
LINK 8: ..//www.webmd.com/../tc/newcastle-disease-virus... (2015-05-28)

Newcastle disease, also known as Asian fowl plague, caused by a virus, is chicken and a variety of poultry acute highly contagious infectious disease, mainly characterized by dyspnea, diarrhea, nervous disorders, mucosal and serosal bleeding. Pathogenic strains showed great differences in the severity of the disease. ..

Newcastle disease virus (NDV) - A type strain for avian paramyxoviruses.
Members of this family have a single stranded, linear, RNA, with an elliptical symmetry.
The total genome is roughly 16,000 nucleotides. Replication of the the virus takes place in the cytoplasm of the host cell.

NDV is a contagious and fatal viral disease affecting most species of birds.
Clinical signs are extremely variable depending on the strain of virus, species and age of bird, concurrent disease, and preexisting immunity. Four broad clinical syndromes are recognized by scientists. They are Viscerotropic velogenic, Neurotropic velogenic, Mesogenic, and Lentogenic.

NDV is so virulent that many birds die without showing any clinical signs.
A death rate of almost 100 percent can occur in unvaccinated poultry flocks.
NDV can infect and cause death even in vaccinated poultry.
Fortunately NDV has not infected domestic chicken flocks in the United States since the last outbreak was eradicated in 1974.

NDV is spread primarily through direct contact between healthy birds and the bodily discharges of infected birds. The disease is transmitted through infected birds' droppings and secretions from the nose, mouth, and eyes. NDV spreads rapidly among birds kept in confinement, such as commercially raised chickens.

High concentrations of the NDV are found in birds' bodily discharges; therefore, the disease can be spread easily by mechanical means. Virus-bearing material can be picked up on shoes and clothing and carried from an infected flock to a healthy one.

NDV can survive for several weeks in a warm and humid environment on birds' feathers, manure, and other materials. It can survive indefinitely in frozen material. However, the virus is destroyed rapidly by dehydration and by the ultraviolet rays in sunlight.

Smuggled pet birds, especially Amazon parrots from Latin America, pose a great risk of introducing NDV into the US. Amazon parrots that are carriers of the disease but do not show symptoms are capable of shedding NDV for more than 400 days.

NDV affects the respiratory, nervous, and digestive systems.
Symptoms are very variable depending on the strain of virus, species of bird, concurrent disease and preexisting immunity. The incubation period for the disease ranges from 2 to 15 days. An infected bird may exhibit the following signs:

Respiratory: sneezing, gasping for air, nasal discharge, coughing
Digestive: greenish, watery diarrhea
Nervousness, depression, muscular tremors, drooping wings,
........ twisting of head and neck, circling, complete paralysis
Partial to complete drop in egg production and thin-shelled eggs
Swelling of the tissues around the eyes and in the neck
Sudden death

Virus: Anellovirus. DNA (TTV, TTMV, TTMDV, PRA, SAV, SealAV, ZcAV) INDEX
http://www.ncbi.nlm.nih.gov/../PMC2745379/...pdf (2009-09-07)

LINK 2: http://lactobacto.com/tag/anellovirus/ (2015-09-15)
LINK 3:http://lactobacto.com/.../human-microbiome/ (2015-09-15)
LINK 4: http://med.stanford.edu/...virus-could-signal..html (2015-11-21)
LINK 5: http://www.ncbi.nlm.nih.gov/../PMC3511395/ (2012-11-30)
LINK 6: http://www.ncbi.nlm.nih.gov/../PMC2745379/...pdf (2010-12-14)
LINK 7: http://www.sciencedaily.com/../151102143737.htm (2015-11-02)
LINK 8: https://en.wikipedia.org/wiki/Anelloviridae (2015-04)

The Anelloviridae ... are classified as a vertebrate viruses and have a non-enveloped capsid, which is round with isometric, icosahedral symmetry. The type species is torque teno virus (TTV) (genus Alphatorquevirus). The genome is not segmented and contains a single molecule of circular, negative-sense, single-stranded DNA. Three genera of anellovirus are known to infect humans, named TTV, TTMDV, and TTMV.

... healthy newborns have a diversity of viruses in the gut - this is their virome (community of viruses), and it undergoes changes over time. In fact, the entire infant microbiome (community of microbes) is highly dynamic and the composition of bacteria, viruses and bacteriophages changes with age. One interesting finding is that initially newborn babies have a lot of bacteriophages (viruses that infect bacteria), but that these decline over the first two years of age.

( Fever in children was studied and) There was a striking correlation between the height of the maximum temperature and the frequency of TTV and TTMDV infection. Fewer than half of children with maximum temperatures of 38-38.5 C were positive for TTV or TTMDV DNA. In contrast, nearly 100% of children with a maximum temperature of 40 C or higher were infected with TTV or TTMDV. The presence of TTMV DNA did not have a similar correlation with maximum temperature as TTV and TTMDV. Regardless of the height of the maximum temperature, 80-90% of febrile children were infected with TTMV.

After grouping our patient cohort into 6 month age blocks we found that the percentage of anellovirus-positive specimens rose as age increased and peaked at 19-24 months, after which the percent of positive specimens declined. The trend was striking in the TTV and TTMDV-positive plasma and NP specimens and modest in the TTMV-positive plasma and NP specimens. This was a surprising finding because research in the anellovirus field has shown that they are chronic, replicating viruses, with no evidence that they are cleared from body or enter into a latent life cycle phase. We saw the same trend in plasma and NP specimens tested for all three human anellovirus species. ...

TTV and TTMDV could be causing fevers in children, but we believe it is more likely that fever brought on by other means is creating a permissive environment for anellovirus replication or decreasing the clearance of the viruses. The combination of an inflammatory environment and a weakened immune system could alter the replication and degradation dynamics affecting infection, proliferation, and stability of TTV and TTMDV. ... Children were excluded if they had an underlying condition that predisposed them to infection, including cancer, immune deficiency, immunosuppressive therapy, cystic fibrosis, sickle-cell disease, or presence of an indwelling venous catheter. Children with a positive rapid test for influenza also excluded.

A characteristic feature of anelloviruses is the extreme diversity found both within and between anellovirus species; they can exhibit as much as 33%-50% divergence at the nucleotide level. Despite the nucleotide sequence diversity, anelloviruses share conserved genomic organization, transcriptional profiles, a non-coding GC rich region, and sequence motifs resulting in shared virion structure and gene functions. High viral titers found in patient specimens suggest that anelloviruses (may) cause chronic, persistent infection for life.

A study in Japan found that 75-100% of patients tested were infected with at least one of the three human anelloviruses, and many were infected with multiple species. Anelloviruses can infect young children, with the earliest documented infections occurring within the first months of life. These viruses have been found in nearly every body site, fluid, and tissue tested including blood plasma, serum, peripheral blood mononuclear cells (PBMCs), nasopharyngeal aspirates, bone marrow, saliva, breast milk, feces, as well as various tissues including thyroid gland, lymph node, lung, liver, spleen, pancreas, and kidney. The replication dynamics of anelloviruses are virtually unknown because of the inability to propagate these viruses in culture.

Torque teno virus (TTV) is a circular, single-stranded DNA virus that chronically infects healthy individuals of all ages worldwide. ... About 94% of healthy individuals in Russian population have more than 1000 TTV genome copies per 1 ml of blood. ... TTV viral load neither depends on gender, nor age.

Torque teno virus (TTV) was first discovered in 1997 in Japanese patients with non-A-G transfusion-acquired hepatitis. TTV is a small, non-enveloped virus with a single-stranded, circular DNA genome of negative polarity, 3.4-3.9 Kb in length, containing two bigger (ORF1 and ORF2) and several smaller open reading frames. TTV is currently classified to Circoviridae family. Despite being a DNA virus, TTV demonstrates an extremely wide sequence divergence. At least 16 genotypes with evolutionary distance >0.30 has been described so far.

TTV is an ubiquitous virus revealed in more than 50% of the general human population throughout the world and nearly 90% of pongid populations. Co-infection of single individuals with TTV isolates belonging to one or several phylogenetic groups occurs frequently. TTV was first characterized as a blood-born virus and thus referred to transfusion-transmitted (TT) group of viruses [1]. Recent studies suggested the existence of other ways of transmission including parenteral, sexual, mother-to-child and others.

Using qPCR we demonstrated that 485 out of 512 (94%) healthy individuals have TTV viral load of more than 1000 copies per 1 ml of blood, which corresponds to 94.1% of males and 93.9% of females studied. Considerable part of the (Russian) athletes (39.9%) had viral load about 106 copies per 1 ml of blood (median 2.7 × 106) with maximum about 1010 viral genomes per 1 ml. We failed to detect any correlation between the viral load and the age of tested individuals. Also no difference was detected in viral load for men and women.

... we investigated the association between anelloviruses and fever in pediatric patients 2-36 months of age. We determined that although anelloviruses were present in a large number of specimens from both febrile and afebrile patients, they were more prevalent in the plasma and nasopharyngeal (NP) specimens of febrile patients compared to afebrile controls. Using PCR to detect each of the three species of anellovirus that infect humans, we found that anellovirus species TTV and TTMDV were more prevalent in the plasma and NP specimens of febrile patients compared to afebrile controls.

This was not the case for species TTMV which was found in similar percentages of febrile and afebrile patient specimens. Analysis of patient age showed that the percentage of plasma and NP specimens containing anellovirus increased with age until patients were 19-24 months of age, after which the percentage of anellovirus positive patient specimens dropped. This trend was striking for TTV and TTMDV and very modest for TTMV in both plasma and NPspecimens.

Finally, as the temperature of febrile patients increased, so too did the frequency of TTV and TTMDV detection. Again, TTMV was equally present in both febrile and afebrile patient specimens. Taken together these data indicate that the human anellovirus species TTV and TTMDV are associated with fever in children, while the highly related human anellovirus TTMV has no association with fever.

Emerging viral diseases can cause epidemics in wild animal (harbor seal) populations, ...
diagnosing novel viral infections is difficult, because current viral identification techniques have limited capability for characterizing novel viruses.

Diagnostic methods such as ELISA with antibodies for a specific virus, PCR or microarrays with primers designed for a specific virus or PCR with degenerate primers that amplify a closely related group of viruses are effective methods for detecting close relatives of known viruses, but are limited for identification of new viruses. Viral particle purification and shotgun sequencing (viral metagenomics) has been developed as a method to discover novel viruses with limited sequence similarity to previously described viral families. Recent advances in viral metagenomic techniques have enabled viral discovery directly from animal tissues, such as tumours allowing the investigation of viruses involved in disease of humans or other animals.

Mass mortality of Pacific harbor seals (Phoca vitulina richardsii) occurs sporadically along the coast of California, ... all animals had grossly abnormal lungs, and histological examination of three fresh cases revealed severe pneumonia. Pseudomonas aeruginosa ... Analysis of the viral metagenome revealed sequences with amino acid identity to viruses in the family Anelloviridae, which ... are subgrouped into Torque teno virus (TTV), Torque teno mini virus (TTMV), Torque teno midi virus (TTMDV) and small anellovirus (SAV). Known hosts for anelloviruses include humans, non-human primates and domestic animals. Recent metagenomic analyses have also identified anelloviruses in human blood and sea lions.

The genome organization of SealAV is consistent with that of other anelloviruses ... but, shares limited pairwise identity with the sea lion (Zalophus californianus) anellovirus ZcAv (57 %), Torque teno felis virus Fc-TTV4 (54 %) and feline anelloviruses PRA1 (54 %) and PRA4 (55 %) by optimal pairwise alignment of the complete ORF1 nucleotide sequence in BioEdit.

ORF1 encodes 469 amino acids and has weak amino acid sequence identity to the sea lion anellovirus ZcAv (21 %), Torque teno felis virus Fc-TTV4 (18 %) and feline anelloviruses PRA1 (21 %) and PRA4 (18 %) based on optimal pairwise amino acid alignment in BioEdit.

The N terminus of ORF1 contains an arginine-rich region, with 26 arginine residues in the first 63 amino acids (41 %), which is common in single-stranded DNA animal viruses, including anelloviruses, circoviruses and gyroviruses. The SealAV genome shares extremely low nucleotide sequence identity with all known anelloviruses, preventing its detection with degenerate PCR or microarrays designed based on known genomes.

In contrast to the clustering observed for the pinniped and feline anelloviruses, the host seals (phocids) and sea lions (otariids) are more closely related to dogs (canids) than to cats (felids). Therefore, co-diversification between these anelloviruses and their hosts is not supported. ... It has been suggested that TTV can be involved in respiratory disease complexes or enhance the effects of other pathogens in pigs and humans, but the definitive pathogenicity of anelloviruses remains unknown. ... the fact that these viruses cannot be detected in the blood of infected animals by PCR presents a technical limitation to determining viral prevalence and pathogenicity, since lung biopsies cannot be obtained from healthy individuals.

"We are just beginning to understand the interplay between all the different types of life within our gut," said senior author Lori R. Holtz, MD, assistant professor of pediatrics. "They are not stand-alone communities. We also are seeing that the environment of the infant gut is extremely dynamic, which differs from the relative stability that has been shown in adults."The earliest stool samples were taken at 1-4 days of life, and even at this early time point, Holtz noted, viruses were present.

Analyzing genomic material in the stool samples, the researchers noted that some of the viruses they identified are known to infect cells of the human host, but others actually infect the bacteria. In fact, the researchers found that the kinds of viruses that infect bacteria, not human cells, were the most rich and diverse earliest in an infant's life and then their numbers declined. They also showed that strains of bacteria did the opposite, starting out with low numbers early and becoming more diverse as the babies grew into their toddler years.

The investigators suspect that the changes in population dynamics they observed in these viruses and bacteria are caused by a predator-prey relationship. The viruses that exclusively kill bacteria are called bacteriophage, literally "bacteria eater." The early diversity of bacteriophage means lots of predators with no prey. Since bacteriophage can't survive without their bacterial prey, the high bacteriophage numbers quickly go down. Faced with few predators, bacteria are then free to flourish and colonize the gut. "The predator-prey dynamic is still a hypothesis at this point," Holtz said.

The researchers also observed a relatively large diversity of a type of virus that infects human cells called anellovirus. Anelloviruses are of interest to researchers because they appear to reflect a person's immune status, with more viruses present when the immune system is weaker. "One child had at least 47 anellovirus strains at the 12-month sampling," Holtz said. "It's important to remember that these are healthy children living in the community.

The researchers also noted that almost all of the anelloviruses identified in this study were previously unknown. Such data, originating from only eight babies in St. Louis, hints at the size and difficulty of the task of even determining a healthy baseline for the virome. Such a baseline is required before scientists can understand what roles gut viromes may play in conditions like obesity, diabetes, colitis and Crohn's disease."At this point, we're just trying to establish what is normal," Holtz said.

More than 260,000 Americans are alive today thanks to transplant operations that have replaced their failing kidneys, hearts, lungs or livers with healthy organs donated by volunteers or accident victims. ... Transplant recipients follow strict drug regimens designed to suppress their immune systems just enough to prevent rejection of the donated organ, but not so much as to leave them prone to infection. Until now, maintaining this delicate balance has been something of a medical guessing game. But ... the discovery of what may be a barometer of immune-system strength: a little-known virus that proliferates as the medications suppress the immune system.

The (research) was led by senior author Stephen Quake, PhD, the Lee Otterson Professor in the School of Engineering and professor of Bioengineering and of Applied Physics ... including transplant specialists from the Stanford School of Medicine, isolated specific DNA fragments from the blood of 96 heart and lung transplant patients for the study.

... the microbiome, which is the sum total of all the bacteria, viruses and fungi that inhabit the body. ... these microorganisms unless they cause illness, they help us digest food, excrete waste, make our feet itch or just float around with no discernable effect. In fact, the nonhuman cells that make up the microbiome "outnumber human cells in our bodies at least 10 to one," said lead author Iwijn De Vlaminck, PhD, a postdoctoral scholar in Quake's lab.

... a mysterious micro-organism known as the anellovirus exploded into prominence as the immunosuppressive drugs kicked in, going from very low levels immediately after surgery to dominating the microbiome over time. ... scientists know very little about the anellovirus. Since it was first identified in 1997, it has been found in human subjects whenever scientists have looked for its genetic fingerprints. But this common bug has not yet been identified as the cause of any disease.

But the Stanford scientists did find previous studies involving patients infected with HIV in which levels of anellovirus rose as those unfortunate patients progressed toward AIDS and the full-blown collapse of their immune systems. ... Twenty (studied) patients suffered moderate or severe episodes of organ rejection during the two years of the experiment. In these 20 patients, levels of anellovirus were "significantly lower ... at almost every point in time," the authors write, adding that "the lower viral load observed for rejecting patients is thus indicative of a higher level of immunocompetence." ... lower levels of anellovirus suggest a stronger immune system and an elevated risk of organ rejection, while higher levels of anellovirus suggest a weaker immune system with a corresponding shift in risk toward vulnerability to infection.

Co-senior author Hannah Valantine, MD, professor of cardiovascular medicine and senior associate dean for diversity and leadership at the School of Medicine, described the apparent linkage between anellovirus population and immune system strength as "one of the most exciting observations in my 30-year journey" of transplant research.

"These findings suggest an effective tool to individualize the monitoring and, ultimately, the treatment of rejection," she said. "In the future, this could allow us to safely lower the doses of immunosuppressive drugs patients receive, thereby avoiding devastating side effects."

The microbes living on healthy human skin include bacteria, fungi, and viruses ... but 90% of the viruses found on healthy skin in this study are unknown to researchers - thus "viral "dark matter". The skin virome is the population of viruses on the skin. It turns out that most of the viruses on healthy skin are phage viruses. called bacteriophages. They infect bacteria and may take up residence within bacteria.

... researchers from the Perelman School of Medicine at the University of Pennsylvania have used state-of-the-art techniques to survey the skin's virus population, or "virome." The study, ... reveals that most DNA viruses on healthy human skin are viral "dark matter" that have never been described before. ... Skin-resident bacteria ... help ward off harmful infections, and maintain proper skin immunity and wound-healing, but under certain circumstances they can do the opposite. ...

The most abundant skin-cell infecting virus was human papilloma virus (HPV), which causes common warts and has been linked to skin cancers. However, (90%) of the detected DNA from the VLPs (Virus-like particles) did not match viral genes in existing databases. ... Most of the detected viral DNA appeared to belong to phage viruses, which infect and often take up long-term residence within bacteria. And when Grice and colleagues sequenced skin bacterial DNA from the same 16 subjects, they found that it often contained tell-tale marks -- called CRISPR spacers -- of prior invasion by the same phage viruses.

Although the results suggest that most of our normal skin-resident viruses are in fact resident in our skin bacteria, such viruses can still affect our health via their influence on the microbiome. The Penn researchers found evidence in the phage DNA of genes that could make host bacteria more resistant to antibiotics, for example, or more likely to cause a harmful infection. ... The results also showed that the skin virome varies considerably depending on the body site. ... the virome was most diverse in the crook of the arm, a site that is intermittently exposed and occluded.

Virus: Mouse Minute Parvovirus. DNA (MVM(p), MVM(i), RV, PVR-1) INDEX
http://www.nap.edu/read/1429/chapter/15 (2015)

LINK 2: http://legacy.jyi.org/../volume6/issue2/features/redig.html
LINK 3: http://www.zoologix.com/.../MouseMinute&Parvovirus.htm
LINK 4: http://www.usbio.net/item/209245

KRV is a single-stranded DNA virus, family Parvoviridae, genus Parvovirus.
KRV is the type species of the genus. It is synonymous with rat virus (RV) and parvovirus r-1.
Approximately a dozen strains of the virus have been isolated. The virion is non-enveloped, and measures 18-30 nm in diameter. The genus Parvovirus presently contains 13 distinct serotypes, three of which occur in rodents: KRV, H-1 virus, and Minute Virus of Mice.

Parvoviruses are remarkably resistant to environmental conditions.
Infectivity is retained after heating at 80°C for 2 hours or 40°C for up to 60 days.
They also are resistant to dessication, pH 2 to 11, chloroform, ether, and alcohol.

The significance of minute virus of mice (MVM) is uncertain.
It has little significance for most studies, but may be highly significant for studies involving mouse transplantable tumors, leukemias, and in vitro immunoassays. ... it was identified as a prevalent indigenous infection in mouse colonies, and as one of the most common contaminants of mouse leukemia virus stocks and transplantable tumors. Two strains of the virus MVM(p) and MVM(i) have been of particular interest to molecular biologists.

The virion of MVM measures 26 nm in diameter, has an icosahedral capsid with 32 capsomeres, and is non-enveloped. The complete nucleotide sequence of the genome is 5081 nucleotides long. The genome encodes for three proteins that make up the viral capsid, VP-1, VP-2, and VP-3, plus two nonstructural proteins, NS-1 and NS-2 for which the function is uncertain.

MVM is highly contagious.
Virus is shed in the urine and feces.
Fomites such as contaminated food and bedding are particularly important because the virus is very resistant to environmental conditions. Nasal-oral contact is also effective in transmission but aerosols are probably not important because uninfected mice in cages eight inches away from infected mice do not become infected. Maternal antibody is protective until 6 to 8 weeks of age but most mice in infected colonies become infected by two or three months of age.

Serologic methods are used for routine health surveillance.
The enzymelinked immunosorbent assay and the immunofluorescent antibody test are considered most sensitive. Mice of the MRL/MpJ strain are reported to give frequent false positive HAI test results for MVM. Transplantable tumors and other biologic materials from mice can be screened by the mouse antibody production (MAP) test and/or virus isolation. The HAI, CF, and NT tests can be used in situations where discrimination between MVM, Kilham rat virus, and H-1 virus infection is desired.

Infection can become established in a colony through introduction of contaminated transplantable tumors, virus stocks, and other biologic materials that are passaged in mice. All such materials should be monitored for MVM and other infectious agents before admission to a facility. Considerable evidence that MVM can interfere with research has come from studies of MVM(i), a single variant of the virus that may or may not occur as a natural infection in contemporary mice. MVM(i) grows lytically in cytotoxic T-lymphocyte clones, abrogates cytotoxic T-lymphocyte responses, suppresses T-lymphocyte mitogenic responses and suppresses T helper-dependent B-lymphocyte responses, in vitro.

The intramuscular inoculation of MVM(p) into mice suppresses the growth of Ehrlich ascites tumor cells given intraperitoneally.

Virus: Polyoma virus. DNA (MPV, BKV, JCV, SV40, PyV, RPV, BFD ..) INDEX
https://en.wikipedia.org/wiki/Polyomaviridae

LINK 2: http://www.avianbiotech.com/Diseases/Polyoma.htm
LINK 3: http://virology-online.com/.../polyomaviruses.htm
LINK 4: http://microbewiki.kenyon.edu/../Human_JC_Polyomavirus
LINK 5: http://www.zoologix.com/.../MousePolyoma.htm
LINK 6: ..emergingworlds.com/..POLYOMAVIRUSES..HUMAN_TUMORS...htm (1999)
LINK 7: http://avianmedicine.net/.../2013/03/32.pdf (2013)
LINK 8: http://www.usbio.net/item/209245
LINK 9: http://www.nap.edu/read/1429/chapter/15 (2015)

Polyoma virus is a DNA virus, family Papovaviridae, genus Polyoma virus.
The Papovaviridae family is comprised of two genera: Polyomavirus and Papillomavirus.
Their genomes consist of a single copy of a double-stranded, covalently closed, circular, supercoiled DNA and average about 5 kilobases in length. Polyomaviruses are small DNA viruses that typically establish persistent but inapparent infections of their natural hosts, although cytolytic disease may develop if the host becomes immunocompromised. Mouse polyoma virus is the type species of the genus. It is related to K virus, simian virus 40, rabbit kidney vacuolating virus, and others. The virion is spherical, measures 44 nm in diameter, and icosahedral. It is highly resistant to environmental conditions and to physical and chemical agents.

Currently, there are twelve members of the genus Polyomavirus recognized by the International Committee on Taxonomy of Viruses (ICTV). The six best-characterized members of the group are BK virus (BKV), JC virus (JCV), simian virus 40 (SV40), murine polyomavirus (PyV), hamster papovavirus (HaPV), and lymphotropic papovavirus (LPV). The most intensely studied viruses in this group are PyV and SV40. The other six polyomaviruses that are recognized by the ICTV include budgerigar fledgling disease virus (BFDV), bovine polyomavirus (BPyV), another murine polyomavirus [Kilham virus (KV)], baboon polyomavirus 2 (PPV-2), rabbit kidney vacuolating virus (RKV), and simian virus agent 12 (SA12). Rat polyomavirus (RPV) has been reported but is not yet recognized by the ICTV.

Multiple strains have been identified for some but not all members of the genus Polyomavirus.
For example, SV40 strains 776, Baylor, and VA45-54 have been widely used in laboratory studies. Each SV40 strain was derived from an independent isolate of the virus, and DNA sequence polymorphisms in genetically stable regions of the viral genome outside of the viral regulatory region were used to distinguish strains. The avian polyomavirus referred to as BFDV by the ICTV is not a single entity; three distinct viruses can be distinguished based on DNA sequence analysis and clinical studies, and these three viruses are designated BFDV 1-3. In contrast, studies of polyomavirus KV have been based on a single virus isolate.

The circular genomes of all polyomaviruses are superficially arranged in a similar manner, and three general regions can be identified based on function. These are referred to as the regulatory (noncoding) region, the early coding region, and the late coding region. The regulatory region separates the coding regions and contains nucleotide sequences that are necessary for the initiation of viral DNA replication and that govern the balance between early and late transcription. The direction of early and late transcription is divergent, with opposite DNA strands used during these processes.

The prevalence of polyoma virus infection is poorly understood.
The virus is highly contagious. It is shed in urine, saliva, and feces, but excreted in higher titer and for a longer periods of time in urine. In persistently infected dams, the titer of virus in the kidney increases during late pregnancy. The virus has a propensity for airborne dissemination and intranasal infection. Transmission occurs readily within and between cages in the same room. Contaminated feed and bedding can be important sources of infection. Transplacental transmission can occur but only if mice are infected during gestation.

Mammalian polyomavirus infections are typically subclinical and persistent in their natural hosts.
Persistence occurs in multiple organs and for indefinite periods. Unlike their mammalian counterparts, avian polyomaviruses are sometimes agents of clinically apparent diseases. The original BFDV isolate, now referred to as BFDV-1, was recovered from fledgling budgerigars and causes a multisystemic infection with high mortality rates. BFDV-2 was isolated from chickens (but has not yet been associated with disease in chickens), whereas BFDV-3 was isolated from a macaw exhibiting symptoms similar to those observed with BFDV-1 infection. Thus, two of the three known avian polyomaviruses are recognized as agents of acute lethal disease, unlike the usually benign infections caused by mammalian polyomaviruses.

Polyomaviruses in mammals are natural tumor inducers.
There has thus far been no association between polyomavirus infections in birds and an increased incidence of tumors, although more in-depth studies are necessary. Some mammalian polyomavirus infections are known to persist by incorporating viral genome into host cell DNA.

The respiratory tract is generally accepted as the natural route of infection of mice with polyoma virus as smaller amounts of virus are required to establish the infection by this route than by the alimentary route used an in situ hybridization technique to follow the pattern of infection after intranasal infection of neonatal mice. Primary replication of the virus occurred in the nasal mucosa, submaxillary salivary glands, and lungs. This was followed by a systemic phase in which viral replication predominated in lung and liver, and also occurred in kidney and colon around six days post infection. The lungs, kidney, and colon appeared to be the main portals for exit of the virus.

As a group, polyomaviruses typically reside in a latent state, and infections become patent following periods of suffering from stressors.

The epizootiology of polyomavirus infections is not fully understood.
The factors involved in the duration and induction of viral shedding remain unresolved.
Some asymptomatic adults produce persistently infected young, while others have neonates that intermittently may develop clinical signs and die. It has been suggested that persistently infected birds may be immunotolerant as a result of being infected before they are immunocompetent.

Some birds are known to shed virus in the presence of high antibody titers.
Asymptomatic adults that intermittently shed the virus are thought to be responsible for the persistence, transmission and spread of the virus through various avian populations. In polyomavirus outbreaks involving 23 different budgerigar aviaries, the onset of disease could be traced to the addition of new, clinically normal breeders.

Virus can replicate in the epidermal cells of the feather follicles resulting in the presence of virus in "feather dust," which may enter a susceptible host through the respiratory or gastrointestinal tract. Virus has been isolated from lung tissue supporting the possibility of an aerogenous transmission. The presence of virus in the renal tubular epithelial cells suggests passage of virus in the urine. Polyomavirus nucleic acid can be detected in cloacal swabs taken from birds during polyomavirus outbreaks. The recovery of viral DNA from the cloaca suggests that the virus could be shed from gastrointestinal, renal or reproductive tissues.

The BFD virus can replicate in a variety of target cells of many avian species including chicken embryo cells. The virus appears to require host cells that are dividing and temperatures of at least 39°C. Following the primary viremia, inclusion bodies can develop in most internal organs as well as the skin and developing feathers. The highest virus concentration is usually found in the brain. Tissue lesions can be severe and are directly related to the level of morbidity and mortality. The virus has been associated with immunosuppression through its ability to destroy or inhibit the normal development of lymphoid tissue.

Aviary personnel, technicians, veterinarians, pet owners and any aviary equipment should be considered important vectors for this environmentally stable virus.

There are accumulating reports of the association of polyomaviruses BKV, JCV, or SV40 with certain human tumors. It is striking that all three viruses have been associated with brain tumors, emphasizing a basic neurotropic character of primate polyomaviruses. ...

Athymic (nu/nu) mice given heterotransplants of human tumors contaminated with the virus have been reported to develop a syndrome characterized by wasting and paralysis of the rear legs and tail.

A chronic form of polyomavirus has also been described and is typified by weight loss, intermittent anorexia, polyuria, recurrent bacterial or fungal infections and poor feather formation. Birds that recover appear normal, although some birds have been found to die months later from renal failure.

Pleomorphic salivary gland tumors are the most common lesions occurring in experimentally infected neonatal mice. Sarcomas and carcinomas of the kidney, subcutis, mammary gland, adrenal gland, bone, cartilage, blood vessels, and thyroid also occur. Many are transplantable to syngeneic hosts. Strains of mice differ in their susceptibilities, with those of C57BL and C57BR/cd lineage being among the most resistant and athymic (nu/nu) mice being the most susceptible.

Control of polyoma virus is not likely to be a problem except in those animal facilities where mice are given experimental infections of the virus, transplantable tumors or other biological materials contaminated with the virus are introduced into the facility, or wild mice gain access to the facility and transmit the infection to laboratory mice. Once established in a mouse facility, the infection can spread rapidly to adjacent rooms. If experimental infections of polyoma virus are to be carried out in a facility, rigorous containment measures such as the use of plastic film isolators may be necessary to prevent spread of the infection.

Polyomavirus virions are small, nonenveloped particles that are resistant to severe environmental conditions, many disinfectants and heat at 56°C for two hours. Stability of the virus causes a considerable problem in the aviary because persistently infected adult birds can shed virus in their feather dust or excrement. Manual removal of any organic debris followed by the use of appropriate disinfectants is required to prevent or contain outbreaks.

Outbreaks of polyomavirus tend to be persistent in budgerigar aviaries that utilize a constant breeding cycle, while the disease appears to be self-limiting in aviaries raising larger Psittaciformes where breeding cycles are discontinuous. High levels of fledgling mortality can be reduced in budgerigar aviaries by stopping the breeding cycle and resting the birds for several months.

Natural infections are usually inapparent (polyoma virus-induced tumors have not been reported in naturally infected immunocompetent mice).

Most polyomaviruses have the ability to induce tumor formation when introduced into certain foreign hosts and are considered oncoviruses. Some polyomaviruses, including those that infect humans, have occasionally been detected in cancerous tissue of their natural hosts.

Virus: Norovirus. RNA (NoV, SRSVs, MNV-1) INDEX
http://microbewiki.kenyon.edu/index.php/Norovirus (2010-08-20)

LINK 02: http://www.scielo.br/pdf/ramb/v57n4/en_v57n4a23.pdf
LINK 03: http://www.zoologix.com/../MouseNorovirus.htm
LINK 04: https://en.wikipedia.org/wiki/Norovirus (2015-10-29)
LINK 05: ..//blogs.scientificamerican.com/..survive-for..years../ (2012-01-17)
LINK 06: http://viralzone.expasy.org/all_by_species/194.html (2008)
LINK 07: http://www.thenakedscientists.com/../interview/838/ (2007)
LINK 08: https://www.ncbi.nlm.nih.gov/pubmed/16968608 (2006)
LINK 09: http://www.mayoclinic.org/../norovirus/.. (2014-04-02)
LINK 10: http://jvi.asm.org/content/79/5/2900.full.pdf+html (2005-03)
LINK 11: ..//www.plospathogens.org/../journal.ppat.1002921.. (2012-10-18)
LINK 12: ..//www.plospathogens.org/../journal.ppat.1000108.. (2008-07-18)

Noroviruses (NoV) are a very stable, genetically diverse group of single-stranded RNA, non-enveloped viruses belonging to the Caliciviridae family. It contains a linear, non-segmented, positive-sense RNA genome. According to the International Committee on Taxonomy of Viruses, the genus Norovirus has one species, which is called Norwalk virus.
Serotypes, strains and isolates include:

• Norwalk virus;
• Hawaii virus;
• Snow Mountain virus;
• Mexico virus;
• Desert Shield virus;
• Southampton virus;
• Lordsdale virus;
• Toronto virus;
• Wilkinson virus;
• Winter Vomiting bug;
• "small, round-structured viruses" (SRSVs)

Although noroviruses (NoVs) were the first viral agents linked to gastrointestinal disease, for a long time they have been considered secondary cause of gastroenteritis, second to rotaviruses as etiologic agents. The development of molecular techniques in diagnosing NoV provided a clearer insight into the epidemiological impact of these viruses, which are currently recognized not only as the leading cause of non-bacterial gastroenteritis outbreaks, but also as a major cause of sporadic gastroenteritis in both children and adults.

Currently (2012), most gastroenteritis in children are considered to be caused by viruses included in four different families: Reoviridae (rotavirus), Caliciviridae (norovirus and sapovirus), Astroviridae (astrovirus), and Adenoviridae (adenovirus).

Noroviruses commonly isolated in cases of acute gastroenteritis belong to two genogroups: genogroup I (GI) includes Norwalk virus, Desert Shield virus and Southampton virus; and II (GII), which includes Bristol virus, Lordsdale virus, Toronto virus, Mexico virus, Hawaii virus and Snow Mountain virus.

Noroviruses can genetically be classified into five different genogroups (GI, GII, GIII, GIV, and GV), which can be further divided into different genetic clusters or genotypes. For example, genogroup II, the most prevalent human genogroup, presently contains 19 genotypes. Genogroups I, II and IV infect humans, whereas genogroup III infects bovine species, and genogroup V has recently been isolated in mice.

Most noroviruses that infect humans belong to genogroups GI and GII.
Noroviruses from Genogroup II, genotype 4 (abbreviated as GII.4) account for the majority of adult outbreaks of gastroenteritis and often sweep across the globe. Recent examples include US95/96-US strain, associated with global outbreaks in the mid- to late-1990s; Farmington Hills virus associated with outbreaks in Europe and the United States in 2002 and in 2004; and Hunter virus which was associated with outbreaks in Europe, Japan and Australasia. In 2006, there was another large increase in NoV infection around the globe. Reports have shown a link between the expression of human histo-blood group antigens (HBGAs) and the susceptibility to norovirus infection. Studies have suggested the viral capsid of noroviruses may have evolved from selective pressure of human HBGAs.

A 2008 study suggests the protein MDA-5 may be the primary immune sensor that detects the presence of noroviruses in the body. Some people have common variations of the MDA-5 gene that could make them more susceptible to norovirus infection.

(2006) epidemiologic studies have shown that norovirus is one of the most frequent causes of acute nonbacterial gastroenteritis. Reverse-transcription polymerase chain reaction and nucleotide sequencing (PCR and NS) are the means by which the hundreds of norovirus strains have been identified, named, and classified into genogroups and genetic clusters. They are also the means by which a particular strain is traced from the source of an outbreak throughout its spread. These molecular techniques have been combined with classic epidemiology to investigate norovirus outbreaks in diverse settings, including hospitals, nursing homes, dining locations, schools, daycare centers, and vacation venues. The virus affects around 267 million people and causes over 200,000 deaths each year; these deaths are usually in less developed countries and in the very young, elderly and immunosuppressed.

Outbreaks of norovirus infection often occur in closed or semiclosed communities, such as long-term care facilities, overnight camps, hospitals, schools, prisons, dormitories, and cruise ships, where the infection spreads very rapidly either by person-to-person transmission or through contaminated food. Many norovirus outbreaks have been traced to food that was handled by one infected person. The diagnostic and management approach to an individual patient is to use clinical and epidemiologic findings to rule out "not norovirus." At the first sign that there is an outbreak, strict compliance with cleaning, disinfection, and work release guidelines is important to prevent further spread.

Norovirus infection is common among individuals throughout the world, regardless of economic status, resulting in significant morbidity and loss of productivity. Recent reports (2004) of consecutive norovirus outbreaks on cruise ships, involving hundreds of passengers and crew.

The major obstacles to norovirus vaccine development are the great degree of antigenic heterogeneity within the family, the possibility that immunity to noroviruses may be short-lived, and the lack of understanding of the correlates of protective immunity. An effective vaccine should also provide protective immunity against an ever-growing list of norovirus strains. Evidence from outbreak investigations and human challenge studies suggests that these viruses are highly infectious, yet the biology and immunology of norovirus infection remain poorly understood.

Early human challenge studies demonstrated that some volunteers remained uninfected even when challenged with high doses of NV, suggesting that some individuals may be genetically resistant to NV infection. ... noroviruses (may) use multiple methods for attachment to cells and hence for infection. Short-term immunity to NV has been observed in previous human challenge studies. However, this immunity did not necessarily extend to heterologous virus challenge, as volunteers who became ill upon challenge with NV also became ill upon subsequent challenge with HV (Hawaii Virus) at the same rate as volunteers not previously infected with NV (Norovirus). Further rechallenge studies have shown that long-term immunity is not conferred by a single NV challenge, as some volunteers who were susceptible to an initial NV infection were susceptible to infection in subsequent challenges 27 to 42 months later.

Caliciviruses contain one single piece of single-stranded RNA in a protein capsid with no lipid envelope. Norovirus is the same, and its RNA encodes a mere two proteins, both used in making the capsid. It is utterly amazing to me that something so inconsequentially small and simple could cause such profound misery from such an efficient little package.

If someone calculated a misery per base pair per person infected index, I think norovirus would be right at the top, considering Ebola virus clocks in at just under 19,000 RNA base pairs and might cause a few hundred cases a year at most.., while norovirus contains a mere 7,500 but infects 21 million, hospitalizes 70,000 and kills more than 500 people in the U.S. alone every year. In developing countries, the virus kills about 200,000 children under age five annually.

Norovirus infection is characterized by nausea, projectile vomiting, watery diarrhea, abdominal pain, and in some cases, loss of taste. General lethargy, weakness, muscle aches, headache, and low-grade fever may occur. The disease is usually self-limiting, and severe illness is rare. Although having norovirus can be unpleasant, it is not usually dangerous and most who contract it make a full recovery within a couple of days. Norovirus is rapidly inactivated by either sufficient heating or by chlorine-based disinfectants and polyquaternary amines, but the virus is less susceptible to alcohols and detergents.

... Anyone who's experienced it can tell you it's a bit like having all of your intestines' pain receptors activated at once, with uncontrollable nausea and/or diarrhea added as a special bonus. When I was in high school, every so often I'd experience twelve hours of intense pain along with nausea so powerful that I'd feel the urge to hurl even when nothing was left. This was followed by 12 hours of utter exhaustion. Then, I'd feel pretty much normal again and go right back to school, no doubt perpetuating the cycle since victims shed virus for several days after they recover.

Foodborne infection has been particularly prominent, and the CDC estimates that 40-50% of all U.S. foodborne gastroenteritis outbreaks are caused by norovirus. A wide variety of foods have been implicated, including salads, salad dressings, baked goods, deli meats, fruits and vegetables, water, and ice. Secondary transmission has occurred in most outbreaks, which usually terminate spontaneously after one to two weeks. Transmission appears to occur through fecal-oral spread; respiratory spread has been suspected but never proven. Virus shedding (as assayed by RT-PCR) can last from a few days to several weeks and can begin before symptoms occur and continue after they have resolved, complicating the management of outbreaks. These infections are worldwide in distribution and affect all age groups, although mostly school-aged children and adults.

Norovirus is an important virus to consider because of its biologic, physicochemical, and epidemiologic features, which present serious challenges for infection control. Noroviruses extremely infectious, and as few as 10 to 100 particles may be needed to cause infection. ... norovirus can survive at least 61 days in well water. ... They are highly resistant to inactivation by freezing, heating to 60°C, exposure to chlorine in concentrations of 0.5 to 1.0mg per liter, pH levels of 2.7, and treatment with ether, ethanol, or detergent-based cleaners. It is clear that Norovirus is an environmental threat for humans, with the manifestation of the virus causing mild-severe gastroenteritis.

They are extremely contagious, and fewer than twenty virus particles can cause an infection (some research suggests as few as five). Transmission can be aerosolized when those stricken with the illness vomit, and can be aerosolized by a toilet flush when vomit or diarrhea is present; infection can follow eating food or breathing air near an episode of vomiting, even if cleaned up. The viruses continue to be shed after symptoms have subsided and shedding can still be detected many weeks after infection. The norovirus can survive for long periods outside a human host depending on the surface and temperature conditions: it can stay for weeks on hard surfaces, and up to twelve days on contaminated fabrics, and it can survive for months, maybe even years in contaminated still water. The estimated mutation rate (1.21×10-22 to 1.41 ×10-22 substitutions per site per year) in this virus is high even compared with other RNA viruses.

When a person becomes infected with norovirus, the virus is replicated within the small intestine.
After approximately one to two days, norovirus infection symptoms can appear. The principal symptom is acute gastroenteritis that develops between 12 and 48 hours after exposure, and lasts for 24-72 hours.

Vomiting, in particular, transmits infection effectively, and appears to allow airborne transmission.
In one incident, a person who vomited spread infection right across a restaurant, suggesting that many unexplained cases of food poisoning may have their source in vomit. 126 people were dining at six tables in December 1998; one woman vomited onto the floor. Staff quickly cleaned up, and people continued eating. Three days later others started falling ill; 52 people reported a range of symptoms, from fever and nausea to vomiting and diarrhea. The cause was not immediately identified.

Researchers plotted the seating arrangement: more than 90% of the people at the same table as the sick woman later reported becoming ill. There was a direct correlation between the risk of infection of people at other tables and how close they were to the sick woman. More than 70% of the diners at an adjacent table fell ill; at a table on the other side of the restaurant, the attack rate was still 25%. The outbreak was attributed to a Norwalk-like virus (norovirus). Other cases of transmission by vomit were later identified.

In one outbreak at an international scout jamboree in the Netherlands, each person with gastroenteritis infected an average of 14 people before increased hygiene measures were put in place. Even after these new measures were enacted, an ill person still infected an average of 2.1 other people. A CDC study of 11 outbreaks in New York State lists the suspected mode of transmission as person-to-person in seven outbreaks, foodborne in two, waterborne in one, and one unknown. The source of waterborne outbreaks may include water from municipal supplies, wells, recreational lakes, swimming pools and ice machines.

Shellfish and salad ingredients are the foods most often implicated in norovirus outbreaks.
Ingestion of shellfish that have not been sufficiently heated poses a high risk for norovirus infection.
Foods other than shellfish may be contaminated by infected food handlers.

A non-functional fucosyltransferase FUT2 provides high protection from the most common norovirus GII.4. Functional FUT2 fucosyltransferase transfers a fucose sugar to the end of the Histo-blood group ABO(H) precursor in gastrointestinal cells and saliva glands. The ABH antigen produced is thought to act as receptors for human norovirus. Homozygous carriers of any nonsense mutation in the FUT2 gene are called non-secretors, as no ABH antigen is produced. Approximately 20% of Caucasians are non-secretors due to the G428A and C571T nonsense mutations in FUT2 and therefore have strong although not absolute protection from the norovirus GII.4. Non-secretors can still produce ABH antigens in erythrocytes, as the precursor is formed by FUT1. Some norovirus genotypes (GI.3) can infect non-secretors. Of individuals who are secretor positive, those with blood type O were more likely to be infected and B less likely.

If your family includes young children, it's a good idea to have commercially prepared oral hydration solution, such as Pedialyte, on hand. Adults can drink sports drinks and broths. Drinking liquids that contain a lot of sugar, such as soft drinks and fruit juices, can make diarrhea worse.

Smaller meals and a bland diet may help limit vomiting.

    Soup
    Starches and cereals, such as potatoes, noodles, rice or crackers
    Banana
    Yogurt
    Broiled vegetables

Several groups of viruses may infect persons after ingestion and then are shed via stool.
Of these, the norovirus (NoV) and hepatitis A virus (HAV) are currently recognised as the most important human foodborne pathogens with regard to the number of outbreaks and people affected in the Western world. NoV and HAV are highly infectious and may lead to widespread outbreaks.

The clinical manifestation of NoV infection, however, is relatively mild.
Asymptomatic infections are common and may contribute to the spread of the infection.
Introduction of NoV in a community or population (a seeding event) may be followed by additional spread because of the highly infectious nature of NoV, resulting in a great number of secondary infections (50% of contacts).

Most documented foodborne viral outbreaks can be traced to food that has been manually handled by an infected foodhandler, rather than to industrially processed foods. The viral contamination of food can occur anywhere in the process from farm to fork, but most foodborne viral infections can be traced back to infected persons who handle food that is not heated or otherwise treated afterwards. Therefore, emphasis should be on stringent personal hygiene during preparation. ... If viruses are present in foods after processing, they remain infectious in most circumstances and in most foods for several days or weeks, especially if kept cooled (at 4 degrees C). ... For the control of foodborne viral infections, it is necessary to:

Heighten awareness about the presence and spread of these viruses by foodhandlers;
Optimise and standardise methods for the detection of foodborne viruses;
Develop laboratory-based surveillance to detect large, common-source outbreaks at an early stage; and
Emphasise consideration of viruses in setting up food safety quality control and management systems.

... norovirus also has a high mutation rate even by RNA-virus standards.
The further bad news here is that having no fatty-lipid membrane means that the virus isn't killed very well by alcohol or detergents (which break down fats), though bleach and old-fashioned handwashing supposedly work well (Oh, old-fashioned handwashing, is there anything you can't do?). This is not good news for those that rely on alcohol-based hand sanitizers and wipes (something to think about next time you blithely swipe an alcohol-based wipe across the handle of your grocery cart or rub your hands with hand sanitizer). Obviously, this is one insidious virus.

The stomach flu is technically not the flu at all: the flu virus only affects the respiratory tract.
The stomach flu is known scientifically as a norovirus. Norovirus outbreaks are common in locations where people live close together, such as cruise ships, nursing homes, military bases and schools. Antibiotics are ineffective, because they fight bacteria, not viruses. Only recently (2008) have scientists been able to grow noroviruses in the laboratory and study them.

"Our research strongly indicates that MDA-5 is the primary sensor for norovirus infection, but the body's ability to detect the virus is so important that it doesn't just rely on one sensor," says senior investigator Marco Colonna, Ph.D., professor of pathology and immunology. "We found that another protein sensor - TLR3 - serves as a back-up and there may be others that have not yet been discovered."

The team demonstrated their work in mice but says the same proteins are likely responsible for detecting norovirus infection in humans. MDA-5, and to a lesser extent, TLR3, respond by causing other cells to release interferon, which shuts down production of the virus and initiates a full-scale immune attack. MDA-5 and TLR3 are both intracellular proteins. ...

Interestingly, some people have common variations of the MDA-5 gene that could make them more susceptible to norovirus infection, the researchers say. ...

Human Norovirus infects humans.
The virus is specific to certain humans -- this has to do with binding specificity.
Binding specificity is based upon the histo-blood group antigens. Virulence factors include the binding to several histo-blood group antigens (complex carbohydrate structures expressed on many cell types, including gastrointestinal epithelial cells; three distinct antigens exist: A, B, and O). Different viral genotypes have different affinity for ABO antigens. GI noroviruses preferentially recognize blood group antigens A and O. GII noroviruses preferentially recognize blood group antigens A and B. ... human blood group type is closely linked to susceptibility to norovirus gastroenteritis.

Upon infection with Norovirus, lesions in the jejunum but not the stomach or rectum and manifests with vomiting and diarrhea. Changes appear within 24 hours of viral infection and remain through the height of the illness, persisting for a variable time after the illness. Intestinal villi appear blunted, but the mucosa remains intact. Symptoms that usually accompany Norovirus-induced illness usually entails both vomiting and diarrhea, and is often accompanied by nausea, abdominal cramps, and systemic symptoms such as malaise, myalgia, chills, and headaches. Fever is present in approximately half the cases and is usually low-grade. The illness typically has an incubation period of 24-51 hours. The actual viral mechanisms, which cause vomiting and diarrhea are unknown.

Noroviruses and other caliciviruses are unique among the animal viruses because they posses a capsid composed of a single major structural protein. Because of this, all the functional entities required for calicivirus structural integrity, immunogenicity, and infectivity are encoded in one structural protein.

It is believed that the capsid protein not only provides shell structure for the virus but also contains cellular receptor binding site(s) and viral phenotype or serotype determinants. The function of VP2 associates with upregulation of VP1 expression in cis and stabilization of VP1 in the virus structure. Understanding the structure and functions of this viral capsid protein should facilitate the development of antiviral strategies for caliciviruses.

... noroviruses can infect and replicate in a physiologically relevant 3-dimentional organoid model of human small intestine epithelium. ... alpha interferon (IFN-a) effectively inhibited the replication of Norovirus in these cells.

IFN-y also inhibited the replication of Norovirus in the replicon-bearing cells. ... the combination of IFN-y and ribavirin showed additive effects in the inhibition of Norovirus replication. Their findings indicated that IFNs and ribivirin may be good therapeutic options for noroviral gastroenteritis (Chang and George, 2007).

Snow Mountain Virus (SMV) infection, in contrast to Norwalk virus (NV), was not dependent upon blood group secretor status. For the majority of volunteers (test subjects), both infected and uninfected, PBMCs stimulated with norovirus virus-like particles secreted IFN-5 and other Th1 cytokines, suggesting previous norovirus exposure in most volunteers. Like the IgG antibodies, the SMV-activated T cells were cross-reactive with HV (Hawaii Virus) but not NV.

Mouse norovirus was first identified in 2003.
Immunocompetent mice infected with the virus can develop transient infection with a short duration of fecal shedding of the virus. Mice that are immunocompromised, including some knockout strains, can develop lethal infection.

Murine norovirus-1 (MNV-1) is one of several murine noroviruses isolated from research mouse facilities and has been used as a model of human norovirus infection. MNV-1 infection has been shown to require components of innate and adaptive immunity for clearance; however, the initial host protein that recognizes MNV-1 infection is unknown. To understand how the host responds to norovirus infection, we studied two classes of proteins, both of which are thought to detect signs of viral infection. We discovered that one of these proteins, melanoma differentiation associated protein-5 (MDA-5), is responsible for detecting a mouse norovirus that is genetically related to the human pathogen.

INDEX