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: Common Characteristics. INDEX
http://encyclopedia2.thefreedictionary.com/encephalomyocarditis+virus
McGraw-Hill Concise Encyclopedia of Bioscience. © 2002
The Columbia Electronic Encyclopedia - Copyright © 2013

LINK 02: http://www.nativeremedies.com/../types-of-viral-infections.html
LINK 03: http://emedicine.medscape.com/../300455-overview (2015-01-13)
LINK 04: http://ratguide.com/health/basics/signs_of_pain_in_rats.php
LINK 05: http://icwdm.org/handbook/damage/WildlifeDiseases.asp
LINK 06: http://www.isb-sib.ch/ -- Swiss Institute of Bioinfomatics.
LINK 07: ..emergingworlds.com/..POLYOMAVIRUSES_AND_HUMAN_TUMORS...htm (1999)
LINK 08: http://viralzone.expasy.org/all_by_species/996.html -- Archives
LINK 09: http://www.ncbi.nlm.nih.gov/../PMC3511395/ (2012-11-30)
LINK 10: http://jvi.asm.org/content/71/6/4531.abstract (1987-06)

Any of a heterogeneous class of agents that share 3 characteristics:

(1) They consist of a nucleic acid genome surrounded by a protective protein shell, which may itself be enclosed within an envelope that includes a membrane;

(2) they multiply only inside living cells, and are absolutely dependent on the host cells' synthetic and energy-yielding apparatus;

(3) the initial step in multiplication is the physical separation of the viral genome from its protective shell, a process known as uncoating, which differentiates viruses from all other obligatorily intracellular parasites.

In essence, viruses are nucleic acid molecules, that is, genomes that can enter cells, replicate in them, and encode proteins capable of forming protective shells around them. Terms such as "organism" and "living" are not applicable to viruses. It is preferable to refer to them as functionally active or inactive rather than living or dead.

Viruses are little packages of DNA or DNA's henchman RNA wrapped in a protein and/or fatty lipid coat. The protein coat, if it exists, is referred to as a "capsid", and individual virus particles are "virions". When present, lipid coats are more or less like our own cell membranes, and are often stolen from them by the virus.

The primary significance of viruses lies in two areas.

First, viruses destroy or modify the cells in which they multiply; they are potential pathogens capable of causing disease. Many of the most important diseases that afflict humankind, including rabies, smallpox, poliomyelitis, hepatitis, influenza, the common cold, measles, mumps, chickenpox, herpes, rubella, hemorrhagic fevers, and the acquired Immunodeficiency syndrome (AIDS) are caused by viruses. Viruses also cause diseases in livestock and plants that are of great economic importance.

Second, viruses provide the simplest model systems for many basic problems in biology.
Their genomes are often no more than one-millionth the size of, for example, the human genome; yet the principles that govern the behavior of viral genes are the same as those that control the behavior of human genes. Viruses thus afford unrivaled opportunities for studying mechanisms that control the replication and expression of genetic material.

Although viruses differ widely in shape and size, they are constructed according to certain common principles. Basically, viruses consist of nucleic acid and protein. The nucleic acid is the genome which contains the information necessary for virus multiplication and survival, the protein is arranged around the genome in the form of a layer or shell that is termed the capsid, and the structure consisting of shell plus nucleic acid is the nucleocapsid.

Some viruses are naked nucleocapsids.
In others, the nucleocapsid is surrounded by a lipid bilayer to the outside of which "spikes" composed of glycoproteins are attached; this is termed the envelope. The complete virus particle is known as the virion, a term that denotes both intactness of structure and the property of infectiousness.

The mechanism of viral transmission varies with the type of virus.
Routes include large-droplet spread over short distances (< 1 m), hand contact with contaminated skin and fomites and subsequent inoculation onto the nasal mucosa or conjunctiva (e.g., rhinovirus, RSV), and small-particle aerosol spread (e.g., influenza, adenovirus). Some viruses are extremely fastidious, whereas others have the capability of surviving on environmental surfaces for as long as 7 hours, on gloves for 2 hours, and on hands for 30 minutes.

A number of viruses, including adenoviruses, influenza virus, measles virus, PIV, RSV, rhinoviruses, and VZV, are easily transmitted during hospital stays and cause nosocomial pneumonia. Adenoviruses, influenza viruses, PIV, and RSV account for 70% of nosocomial pneumonias due to viruses.

Viral genomes are astonishingly diverse.
Some are DNA, others RNA; some are double-stranded, others single-stranded; some are linear, others circular; some have plus polarity, other minus (or negative) polarity; some consist of one molecule, others of several (up to 12). They range from 3000 to 280,000 base pairs if double-stranded, and from 5000 to 27,000 nucleotides if single-stranded.

Viral genomes encode three types of genetic information.

First, they encode the structural proteins of virus particles.

Second, most viruses encode enzymes capable of transcribing their genomes into messenger RNA molecules that are then translated by host-cell ribosomes, as well as nucleic acid polymerases capable of replicating their genomes; many viruses also encode nonstructural proteins with catalytic and other functions necessary for virus particle maturation and morphogenesis.

Third, many viruses encode proteins that interact with components of host-cell defense mechanisms against invading infectious agents. The more successful these proteins are in neutralizing these defenses, the more virulent viruses are.

The two most commonly observed virus-cell interactions are the lytic interaction, which results in virus multiplication and lysis of the host cell; and the transforming interaction, which results in the integration of the viral genome into the host genome and the permanent transformation or alteration of the host cell with respect to morphology, growth habit, and the manner in which it interacts with other cells. Transformed animal and plant cells are also capable of multiplying; they often grow into tumors, and the viruses that cause such transformation are known as tumor viruses.

In general, viral infections remain untreatable.
Non-specific supportive care, antimicrobials to prevent secondary bacterial and fungal infections and good nutritional support, including the supplementation of vitamin C, remain the only available therapeutic regimens for most viral infections. Newly emerging concepts in the use of antisense RNA will undoubtedly result in more specific therapies for many infectious diseases. Interferon has been suggested for treatment of viral infections. Paramunity inducers have proven effective with some viral diseases.

Antiviral agents on which much interest is focused are the interferons.
Interferons are cytokines or lymphokines that regulate cellular genes concerned with cell division and the functioning of the immune system. Their formation is strongly induced by virus infection; they provide the first line of defense against viral infections until antibodies begin to form. Interferons interfere with the multiplication of viruses by preventing the translation of early viral messenger RNAs. As a result, viral capsid proteins cannot be formed and no viral progeny results.

In addition to antibody-producing B cells, T cells play an important role in the control of viral pathogens. The cytokines secreted by antigen-specific CD4-9 helper T cells guide the adaptive immune response. T helper 1 (Th1) and Th2 responses can be activated by both the same and different epitopes within the same pathogen, but one response type will often dominate over the other.

A Th2-favored immune response is primarily characterized by interleukin 4 (IL-4) and IL-10 secretion by CD4-9 cells, resulting in production of IgG2 and other anti-inflammatory factors. A Th1-favored response is primarily characterized by secretion of gamma interferon (IFN-5) by CD4-9 cells, resulting in macrophage activation, B-cell differentiation to IgG1 synthesis, and support for cytotoxic T lymphocytes (CTLs). CTLs are important in the control of human Immunodeficiency virus (HIV) (4), Epstein-Barr virus, influenza virus, lymphocytic choriomeningitis virus, and numerous other viruses.

There is little that can be done to interfere with the growth of viruses, since they multiply within cells, using the cells' synthetic capabilities. The process, interruption of which has met with the most success in preventing virus multiplication, is the replication of viral genomes, which is almost always carried out by virus-encoded enzymes that do not exist in uninfected cells and are therefore excellent targets for antiviral chemotherapy. Another viral function that has been targeted is the cleavage of polyproteins, precursors of structural proteins, to their functional components by virus-encoded proteases; this strategy is being used with some success in AIDS patients.

By far the most effective means of preventing viral diseases is by means of vaccines.
There are two types of antiviral vaccines, inactivated virus vaccines and attenuated active virus vaccines. Most of the antiviral vaccines currently in use are of the latter kind. The principle of antiviral vaccines is that inactivated virulent or active attenuated virus particles cause the formation of antibodies that neutralize a virulent virus when it invades the body.

Most viruses are too small (100-2,000 Angstrom units) to be seen with the light microscope and thus must be studied by electron microscopes. In one stage of their life cycle, in which they are free and infectious, virus particles do not carry out the functions of living cells, such as respiration and growth; in the other stage, however, viruses enter living plant, animal, or bacterial cells and make use of the host cell's chemical energy and its protein- and nucleic acid-synthesizing ability to replicate themselves.

The existence of submicroscopic infectious agents was suspected by the end of the 19th cent.; in 1892 the Russian botanist Dimitri Iwanowski showed that the sap from tobacco plants infected with mosaic disease, even after being passed through a porcelain filter known to retain all bacteria, contained an agent that could infect other tobacco plants. In 1900 a similarly filterable agent was reported for foot-and-mouth disease of cattle. In 1935 the American virologist W. M. Stanley crystallized tobacco mosaic virus; for that work Stanley shared the 1946 Nobel Prize in Chemistry with J. H. Northrup and J. B. Summer. Later studies of virus crystals established that the crystals were composed of individual virus particles, or virions. By the early 21st cent. the understanding of viruses had grown to the point where scientists synthesized (2002) a strain of poliovirus using their knowledge of that virus's genetic code and chemical components required.

Viral Structure
Typically the protein coat, or capsid, of an individual virus particle, or virion, is composed of multiple copies of one or several types of protein subunits, or capsomeres. Some viruses contain enzymes, and some have an outer membranous envelope. Many viruses have striking geometrically regular shapes, with helical structure as in tobacco mosaic virus, polyhedral (often icosahedral) symmetry as in herpes virus, or more complex mixtures of arrangements as in large viruses, such as the pox viruses and the larger bacterial viruses, or bacteriophages.

Certain viruses, such as bacteriophages, have complex protein tails.
The inner viral genetic material -- the nucleic acid -- may be double stranded, with two complementary strands, or single stranded; it may be deoxyribonucleic acid (DNA) or ribonucleic acid (RNA). The nucleic acid specifies information for the synthesis of from a few to 50 different proteins, depending on the type of virus.

Viral Infection of a Host Cell
A free virus particle may be thought of as a packaging device by which viral genetic material can be introduced into appropriate host cells, which the virus can recognize by means of proteins on its outermost surface. A bacterial virus infects the cell by attaching fibers of its protein tail to a specific receptor site on the bacterial cell wall and then injecting the nucleic acid into the host, leaving the empty capsid outside. In viruses with a membrane envelope the nucleocapsid (capsid plus nucleic acid) enters the cell cytoplasm by a process in which the viral envelope merges with a host cell membrane, often the membrane delimiting an endocytic structure.

Within the cell the virus nucleic acid uses the host machinery to make copies of the viral nucleic acid as well as enzymes needed by the virus and coats and enveloping proteins, the coat proteins of the virus. The details of the process by which the information in viral nucleic acid is expressed and the sites in the cell where the virus locates vary according to the type of nucleic acid the virus contains and other viral features. As viral components are formed within a host cell, virions are created by a self-assembly process; that is, capsomere subunits spontaneously assemble into a protein coat around the nucleic core. Release of virus particles from the host may occur by lysis of the host cell, as in bacteria, or by budding from the host cell's surface that provides the envelope of membrane-enveloped forms.

The genetic background of an individual can significantly influence the outcome of viral infection.
Identification of genes involved in susceptibility or resistance to viruses has increased our understanding of many viral disease processes. ... approaches have revealed specific host proteins involved in susceptibility to both RNA and DNA viruses, such as West Nile virus and mouse CMV.

Entry is the first interaction of the virus with its host cell.
It has been shown that viruses can use proteins or oligosaccharides as host receptors, such as influenza virus that uses sialic acids as the receptor or poliovirus that uses a glycoprotein. A virus could use two separate receptors during entry, as shown by human immunodeficiency virus that uses CD4 as the initial receptor and the chemokine receptor, CCR5, as the second receptor. In rhinoviruses, two types of receptors are used by different members of the same virus family that are divided into major and minor groups. TMEV presents a new scenario in which the same family of viruses binds to the same glycoprotein receptor but in different ways. The binding of the demyelinating persistent group is dependent on the interaction with both a sialyl moiety and the protein surface of the receptor, while the nonpersistent group is only dependent on the interaction with the protein surface of the receptor, even though the two groups bind to the same receptor competitively.

Some viruses do not kill host cells but rather persist within them in one form or another.
For example, certain of the viruses that can transform cells into a cancerous state are retroviruses; their genetic material is RNA but they carry an enzyme that can copy the RNA's information into DNA molecules, which then can integrate into the genetic apparatus of the host cell and reside there, generating corresponding products via host cell machinery. Similarly, in bacterial DNA viruses known as temperate phages, the viral nucleic acid becomes integrated into the host cell chromosomal material, a condition known as lysogeny; lysogenic phages are similar in many ways to genetic particles in bacterial cells called episomes.

Viral Diseases
Some human diseases are apparently caused by the body's response to virus infection: immune reaction to altered virus-infected cells, release by infected cells of inflammatory substances, or circulation in the body of virus-antibody complexes are all virus-caused immunological disorders. Viruses cause many diseases of economically important animals and plants, some transmitted by carriers such as insects. A retrovirus (HIV) causes AIDS, several viruses (e.g. Epstein-Barr virus, human papillomavirus) cause particular forms of cancer in humans, and many have been shown to cause tumors in animals. Other viruses that infect humans cause measles, mumps, smallpox, yellow fever, rabies, poliomyelitis, influenza, and the common cold.

The techniques of molecular biology and genetic engineering have made possible the development of antiviral drugs effective against a variety of viral infections. Viruses, like bacterial infective agents, act as antigens in the body and elicit the formation of antibodies in an infected individual. Indeed, vaccines against viral diseases such as smallpox were developed before the causative agents were known. Some viruses stimulate cellular production of interferon, which inhibits viral growth within the infected cell.

Fever is one of the most common reasons children go to the emergency department, resulting in over 5.6 million visits (USA) in 2007. In the past, bacteremia was a common source of fever in children. The recent development of Haemophilus influenzae and Streptococcus pneumoniae vaccines have reduced the frequency of serious bacterial infections in children, making bacteremia an uncommon cause of fever. Localized bacterial infection, such as urinary tract infections, cause 5-10% of fevers in children, but there remains a large percentage of febrile children in which the source of their fever is never identified.

Viral illnesses are believed to cause the majority of cases of fever without a source and result in significant morbidity and mortality especially in young children. Viruses such as human herpes virus 6, Epstein-Barr virus, and adenovirus are known to cause fever in children, and advances in molecular diagnostic techniques have led to the discovery of unknown or underappreciated viruses associated with human disease.

When the same virus is detected in normal tissues as in tumors, it must be considered that the virus is present in the neoplastic cells merely as a harmless "passenger". It should not be considered unusual to find polyomavirus DNA in normal tissue, as these agents establish long-term persistent infections. Accepted human oncogenic viruses are commonly detected in normal tissue; examples include human papillomaviruses, which are found in normal and precancerous cervical tissue, and hepatitis B virus, which can be found replicating in nontumorous liver tissue. ... With most viruses, the mere detection of virus presence does not indicate the development of clinical disease; similarly, the presence of an oncovirus in tumor tissue cannot be assumed to be proof of causality.

An additional level of complexity is that viruses may act as cocarcinogens, i.e., cancer development may be influenced by viral infection but require other cofactors as well. This possibility is exemplified by reports of association of SV40 with human mesotheliomas. There is a significant correlation between asbestos exposure and the development of mesotheliomas; it is possible that SV40 accelerates the development of mesotheliomas in asbestos-exposed individuals or that both asbestos and SV40 together are required to induce mesothelioma development in some persons. ... Other agents (such as chemicals) are frequently suspected to be causally related to the same tumors.

Classification
Viruses are not usually classified into conventional taxonomic groups but are usually grouped according to such properties as size, the type of nucleic acid they contain, the structure of the capsid and the number of protein subunits in it, host species, and immunological characteristics.

There are several procedures that can be used to confirm the presence of a viral infection:

1) Isolation of the pathogen from the test material;
2) Demonstration of viral particles or inclusion bodies by histopathology;
3) Demonstration of viral antigen (Ag) in infected tissues using viral-specific antibodies (Ab);
4) Demonstration of viral nucleic acid in infected tissues using viral-specific nucleic acid probes;
5) Indirect demonstration of a viral infection by detection of humoral antibodies.

A viral disease can sometimes be demonstrated by a rise in antibody titers in paired serum samples.
Viral-specific nucleic acid probes are more sensitive than other techniques and allow the detection of small concentrations of virus as well as the ability to detect the presence of viral nucleic acid before substantial histologic changes may have occurred.

PLoS Pathogens -- www.plospathogens.org -- May 2009 -- Volume 5 -- Issue 5 -- e1000416
doi:10.1371/journal.ppat.1000416.s003 (0.09 MB PDF)

Recent advances in molecular detection methods (e.g. viral oligonucleotide microarrays and viral metagenomics approaches) have led to the identification of many new viruses which are detected not only in symptomatic, but equally in individuals without any clinical manifestation. Insight into the potential role of these so-called "orphan" viruses in disease requires a detailed understanding of their genetic diversity and epidemiology.

Classically, the association of an infectious agent with disease had to fulfill Koch's postulates, a concept that is no longer tenable in modern times. The clinical outcome of a virus infection may depend upon the conditions under which the infection is acquired: For example, poliomyelitis was seldom observed under conditions of poor sanitation, congenital rubella syndrome is a consequence of postponed childhood infection and some types of cancer are late events in which certain viruses play a crucial role. Moreover, it requires detailed insight in viral diversity, since it is well known that minor differences in the genetic make-up of viruses can cause major differences in their pathogenicity. The latter holds especially for RNA viruses such as the picornaviruses which due to their high mutation and recombination rates show remarkable genetic plasticity which may lead to serious pathology merely by accident.

... the increased sensitivity of nucleic acid-based techniques confronts the physician with a relatively new phenomenon of co-infection with 2, 3, or even more viruses at a time, making it hard to predict which of these is the culprit, if causing pathology at all. The latter holds not only for these new viruses but also for well known pathogens as enterovirus, parechovirus and adenovirus. Herewith, a picture emerges of a "viral flora" quite similar to the microbiome of intestinal resident bacteria which are largely beneficial to the host, e.g. by competing out pathogenic invaders and playing an active role in shaping an intestinal immune barrier.

A beneficial effect (cross-protection against bacterial invaders) has also been demonstrated for beta- and gamma-herpesviruses in mice. Human cytomegalovirus has probably a similar effect as it changes the T-cell system dramatically, inducing a unique population of effector-memory CD8 T cells with innate-response features. Viruses, however, are, by nature, host-cell invasive microbes (which gut-resident bacteria are not) and a beneficial role of enteric viruses has not been investigated.

Coxsackie B viruses, and probably also other enteric viruses, affect the tight junctions of the intestinal epithelial cells, which are the gatekeepers of the intestine, thereby increasing gut leakiness. The latter is a direct cause of local inflammation, it may alter mucosal immunity in a beneficial way but leakiness has also been associated with chronic inflammatory disease, as type 1 diabetes and celiac disease. Several lines of evidence indicate a role for coxsackie B viruses and other enteric viruses in type 1 diabetes in humans. ..

The development of antivirals reached "the end of the beginning" in 1980, a phrase used by Collier to summarize the intensive and cumbersome research work carried out in the previous 40 years. Currently (1987) there are a few antiviral agents generally accepted as efficacious. But the emergence of new problems, such as non-A and non-B hepatitis and acquired immuno-deficiency syndrome (AIDS), life-threatening infections in patients that are immunocompromised as a result of cancer therapy or organ transplantation, may require the need to increase research towards the control of viral diseases.

Recently (1987) several authors have demonstrated that suramin, a drug used in the therapy of trypanosomiasis, known to inhibit the reverse transcriptase of several animal retroviruses, can be used to protect human T cells in vitro against infectivity and cytopathic effect of HTLV-III. Studies have begun to see if this drug and 21-tungsto-9-antimonate (HPA 23), a polyoxotungstate known for its ability to protect mice against lethal retroviral infections, can be administered to AIDS patients.

Virus: Sendai RNA virus. (SeV), (SEND) INDEX
https://en.wikipedia.org/wiki/Sendai_virus (2015)

LINK 2: http://www.zoologix.com/rodent/Datasheets/Sendai.htm
LINK 3: http://ratguide.com/health/viruses/sendai_virus_sv.php (2015)
LINK 4: http://dora.missouri.edu/mouse/sendai-virus/ (2013)
LINK 5: http://www.criver.com/.../infectious-agents/rm_ld_r_sendai_virus.aspx
LINK 6: http://www.nfrs.org/sendai.html (2015-10-13)
LINK 7: http://www.Lifetechnologies.com/stemcells
LINK 8: http://www.dnavec.co.jp/en/technology/technology1.html
LINK 9: http://www.wikigenes.org/e/mesh/e/20163.html
LINK 10: http://what-when-how.com/molecular-biology/sendai-virus-molecular-biology/

Recommended Testing Facilities:

IDEXX RADIL, Univ. of Missouri, Columbia, MO: http://IDEXX RADIL.missouri.edu/

Charles River Laboratories, Wilmington, MA: (800) 338-9680

Sendai virus (SeV), also known as murine parainfluenza virus type 1 or hemagglutinating virus of Japan (HVJ), is a negative sense, single-stranded RNA virus of the family Paramyxoviridae, a group of viruses featuring, notably, the genera Morbillivirus and Rubulavirus. SeV is a member of the paramyxovirus subfamily Paramyxovirinae, genus Respirovirus, members of which primarily infect mammals. SV infection may cause high morbidity (illness) and mortality rates when combined with bacterial pathogens such as mycoplasma pulmonis and CAR (cilia associated respiratory) bacillus. The secondary infection may also be caused by bacteria that are non pathogenic until the immune system is depressed, such as, pasteurella.

The virus particles are 150 nm or more in diameter, and they are pleomorphic but usually spherical in shape. The genome is a single molecule of linear, single-stranded, negative-sense RNA of 15,384 nucleotides. The genome RNA is tightly associated with the nucleocapsid (N) subunit proteins and RNA polymerase, which consists of a phosphoprotein (P) and a large (L) protein, forming a helical ribonucleoprotein complex (RNP) or nucleocapsid.

The virion consists of the RNP surrounded by a lipid envelope, which is derived from the host cell plasma membrane and contains two virus-specific glycoproteins, the hemagglutinin-neuraminidase (HN) and the fusion (F) protein. These glycoproteins are present as homooligomers, forming spike-like projections of 8 nm in length. HN binds to the receptor sialic acid residues on the host cell surface, whereas the F protein facilitates virus entry by mediating fusion of the viral envelope with the host cell plasma membrane. F is derived from the biologically inactive precursor F0 glycoprotein through proteolytic processing by a host cell endoproteinase. There is a matrix (M) protein layer between the envelope and RNP. The M protein is important for assembly and stabilization of the virion structure.

The genes encoding the individual proteins are organized in the viral genome in the order 3\u2032-leader-N-P-M-F-HN-L-trailer-5\u2032. The short terminal leader and trailer regions contain the promoters for replication. The RNP, but not the naked RNA, can serve as template for both transcription and replication. The RNA polymerase enters the 3' terminal region and generates each mRNA successively by a stop-start mechanism controlled by the specific cis-acting signals present at each gene boundary. Therefore, the viral gene expression is generally monocistronic, although expression of the P gene is a notable exception. The P messenger RNA directs the synthesis of not only P protein, but also a nested set of accessory proteins, C', C, Y1, and Y2, collectively referred to as C proteins, by using multiple initiation codons in the +1 reading frame relative to that of P.

The P gene further generates an mRNA encoding another accessory protein, V, by cotranscriptional RNA editing featuring the insertion of a single guanine residue at a specific site. The P and V proteins thus have the same amino-terminus but differ in their carboxyl-terminal halves. After translation of the mRNAs and accumulation of viral proteins, the same RNA polymerase copies the same RNP template, but somehow ignores all junction stop-start signals and the editing site, to generate antigenomic RNP with a full-length positive strand RNA. This RNA serves as the template to generate genomic RNP. All replication steps take place in the cytoplasm, and maturation occurs by budding from the plasma membrane.

SeV is responsible for a highly transmissible respiratory tract infection in mice, hamsters, guinea pigs, rats, and occasionally pigs, with infection passing through both air and direct contact routes. The virus can be detected in mouse colonies worldwide, generally in suckling to young adult mice. Epizootic infections of mice are usually associated with a high mortality rate, while enzootic disease patterns suggest that the virus is latent and can be cleared over the course of a year. Sublethal exposure to SeV can promote long-lasting immunity to further lethal doses of SeV. Infection is most devastating to very young, elderly, and immunocompromised rats who may develop a more severe pneumonia and in which the virus may persist for a longer amount of time. Athymic rats (rnu/rnu) are more susceptible to SV and can stay persistently infected.

A novel and well-recognized use for SeV is the fusion of eukaryotic cells, especially to produce hybridoma cells capable of manufacturing monoclonal antibodies in large quantities.

In a natural setting, the respiratory infection of Sendai virus in mice is acute.
From the extrapolation of the infection of laboratory mice, the presence of the virus may first be detected in the lungs 48 to 72 hours following exposure. As the virus replicates in the respiratory tract of an infected mouse, the concentration of the virus grows most quickly during the third day of infection. After that, the growth of the virus is slower but consistent. Typically, the peak concentration of the virus is on the sixth or seventh day, and rapid decline follows that by the ninth day. A fairly vigorous immune response mounted against the virus is the cause of this decline.

The longest period of detected presence of the virus in a mouse lung is fourteen days after infection. SV is a descending respiratory infection. It begins in the nasal passages, and moves through the trachea into the lungs. Sendai causes necrosis of the respiratory epithelium (thin layer of cells on the surface of the organs). In the first few days of infection epithelium necrosis is mild. As the disease progresses the necrosis becomes severe and usually peaks around day 5. By day 9 the regeneration of respiratory tract surface cells occurs. Focal interstitial pneumonia occurs and inflammation and lesions of varying degrees can develop on the lungs.

Those animals which produce subclinical infection because of genetics/previous infection, produce a rapid immune response which prevents lower respiratory tract involvement and thus serious disease. New born rats are passively protected by maternal antibody until they are 4-6 weeks of age, at which time they become infected. New born rats are passively protected by maternal antibody until they are 4-6 weeks of age, at which time they become infected. Once the animal has been infected they normally develop a life long immunity. Adults from populations where this virus is endemic rarely show disease but infection with the virus may give other opportunistic respiratory pathogens which normally aren't doing much, the opportunity they need to cause trouble. It also predisposes rats to develop middle and inner ear disease.

In uncomplicated infection the respiratory system shows evidence of healing within 3 weeks although there may be residual lesions, inflammation, or permanent scarring. Airborne transmission can occur over a distance of 5-6 feet as well as through air handling systems. Transmission by fomites can be reduced by strict hygienic practices. The standard test for Sendai is the ELISA (enzyme-linked immunosorbent assay). IDEXX RADIL offers a newer test: MFI (Multiplex Fluorescent Immunoassay) which is more sensitive. Have your veterinarian contact the testing facility for instructions on collecting and sending the blood sample.

During a viral event broad-spectrum antibiotics are given to the exposed rats to treat the, often fatal, secondary opportunistic bacterial infections. Both doxycycline and Baytril (enrofloxacine) have been used successfully. Usually that approach works well. However, there are times when the bacteria involved is resistant. The Sendai virus is inactivated by UV (ultraviolet) light, temperatures above 37°C (96.8°F), and lipid solvents (such as alcohol).

Health recovery assistance.

• Give Probiotics such as Bene-Bac or yogurt with live active cultures when using antibiotics, to prevent normal gut flora from being destroyed.

• Provide additional warmth to maintain body temperature within normal limits.
  It is essential that the rat does not become overheated or dehydrated.
  The rat should also be able to move away from the heat source if it becomes uncomfortable. If the rat is unconscious or immobile extreme care must be taken to keep the heat low and stable.

• Provide additional nutritional supplements to help maintain strength.

• Provide fluids to prevent dehydration (orally or warmed SQ fluids if necessary).
  Make sure food and water are easily accessible.

• Provide humidification to loosen secretions.
  Provide nebulized breathing treatments if indicated.

Symptoms
• Lethargy
• Sneezing
• Chattering (cold sensitive?)
• Hunched posture
• Respiratory distress
• Labored breathing
• Prolonged pregnancy
• Lack of appetite, weight loss
• Porphyrin discharge from eyes and/or nose
• Failure to thrive in surviving babies and young rats
• Anorexia

Grossly, the lungs of affected mice may be mottled with red and tan foci in the parenchyma (A.).
Histological examination reveals a characteristic interstitial pneumonia with perivascular and peribronchiolar lymphoid infiltrates and hyperplasia of alveolar macrophages (B.). Observation of squamous metaplasia of the bronchial epithelium is associated with the reparative stage of the infection. Lesions in resistant strains resolve quickly and eventually consist of loose peribronchiolar and perivascular lymphocyte cuffs. Commercially available MFI and IFA can be used to identify antibody titers in recovering mice. PCR of lung tissue can be used to diagnose Sendai virus in acute infections. Histologic lesions can be used to help diagnose infection in susceptible mice.

The behavior of SeV was utilized by Köhler and Milstein, who published an article in 1975 outlining a revolutionary method of manufacturing monoclonal antibodies. In need of a reliable method to produce large quantities of a specific antibody, the two merged a monoclonal B cell, exposed to a chosen antigen, and a myeloma tumor cell to produce hybridomas, capable of being grown indefinitely and of producing significant amounts of an antibody specifically targeting the chosen antigen. Though more efficient methods of creating such hybrids have since been found, Köhler and Milstein first used Sendai virus to create their revolutionary cells.

The Sendai virus, used in commercially available kits like the CytoTune® iPS 2.0 Reprogramming Kit, has been shown to be a highly efficient method to reprogram somatic cells into induced pluripotent stem cells. In this video from the Life Technologies innovation showcase at ISSCR 2014, Dr. Laurence Daheron of Harvard Stem Cell Institute discusses the advantages of using non-integrating reprogramming technologies like Sendai virus for effectively transducing a variety of cells.
LINK: http://www.lifetechnologies.com/cytotune

How Does Sendai Virus Reprogram Cells?

Induced pluripotent stem cells (iPSCs) are genetically reprogrammed somatic cells that exhibit a pluripotent stem cell state similar to embryonic stem cells. The discovery in 2006 that human and mouse fibroblasts could be reprogrammed to generate iPSCs with qualities remarkably similar to embryonic stem cells has created a valuable new source of pluripotent cells.

Fibroblasts, similar to other somatic cell types, do not express high levels of the transcription factors Oct4, Sox2, Klf4, and c-Myc under normal conditions. High levels of expression of these four genes will cause reprogramming of the fibroblast and it will become pluripotent.

There are multiple methods to generate iPSCs.
Viruses such as retroviral vectors require integration of the viral genome into the host's chromosomes to express reprogramming genes. Normal gene transcription allows the inserted Oct4, Sox2, Klf4, and c-Myc transgenes to be expressed along with the host's genes. Integration of viral DNA into the host genome disrupts the genome of the cells. This alteration can render the iPSCs and their derivatives less safe for clinical application and can compromise compound screens or disease pathway analyses. On the other hand, Sendai virus is a single stranded negative-sense RNA virus that replicates in the cytoplasm. This means it does not integrate into the host's genome.

Sendai virus replicates independent of cell cycle, unlike other approaches where the exogenous genes are expressed only as the cell divides. Using this strategy, Sendai virus produces very high copy numbers of the target gene. The Cytotune® iPS Sendai Reprogramming Kit contains four Sendai virus-based reprogramming vectors, each expressing one of the four Yamanaka factors Oct4, Sox2, Klf4, and c-Myc.

These viral vectors are added to the dish of cells to be reprogrammed, incubated overnight, and the reprogramming process begins. After reprogramming, quantitative PCR testing shows that the Sendai virus does not remain in the iPSCs, allowing you to perform your research with iPSCs that have no genomic integration or viral remnants. Sendai virus is particularly useful when reprogramming patient derived blood cells, such as CD34 positive cells, T-cells, and PBMCs.

With its non-integrating capabilities, the Sendai virus within the Cytotune®-iPS Sendai Reprogramming Kit allows the use of iPSCs and their derivatives in a broad range of research experiments.

Vectors developed for gene therapy in the past had a fundamental problem; they have to enter cell nucleus as DNA in order to express genes they carry. In the nucleus, some vectors insert themselves into chromosomes (integration), while others may lead to genetic recombination with chromosomal DNA. In fact, there are reports of adverse events (leukemia), although rare, that resulted from the use of retrovirus vectors. Also it is known that, in some cases, adeno-associated virus vectors may cause irreversible alterations to the chromosome structure at the site of integration. Consequently, it has become very important to evaluate carefully the balance between risks and benefits before using these vectors in patients.

In contrast, ID Pharma's Sendai virus vector replicates its genome exclusively in the cytoplasm and produces protein in large quantity. It does not enter cell nucleus. Moreover, Sendai virus genome is made of RNA, a material chemically different from the patient's chromosomal DNA. Therefore, there is no chance in principle that ID Pharma's Sendai virus vector ever alters the chromosomes in the cell nucleus, and thus it is fundamentally free of risks .. associated with other conventional vectors. ... Sendai virus vector-based drugs are effective in a small dosage, and requires less than 5 minutes of vector-cell contact time to introduce genes into cells, over ten-fold shorter (time interval) than that required by other vectors.

... Sendai virus vector is already used for the production of antibodies for research and diagnostic use, production of recombinant proteins, and gene function analyses.

ID Pharma is one of the front-runners in the recombinant RNA virus vector technologies in the world. .. The technologies include the leading-edge technology of efficient construction of "RNA" vector through recombinant "DNA" manipulation, the technology to produce "Intransmissible vector" that can be administered to humans, the technology to control the level of transgene expression in cells, and the technology to produce high-quality vectors suitable for human use. Massive amount of related know-hows have been accumulated, and both master and application patents have already been issued in major countries including Japan, US, Europe, and China.

Virus: Rous RNA sarcoma. (RSV) INDEX
https://en.wikipedia.org/wiki/Rous_sarcoma_virus

LINK 2: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3256973/
LINK 3: http://www.ncbi.nlm.nih.gov/pubmed/6191438
LINK 4: http://.../rous-sarcoma-virus-rsv-molecular-biology/
LINK 5: https://www.youtube.com/channel/UCvxxi7myN2ALKZW5wTrsxaA

Rous sarcoma virus (RSV) is a retrovirus and is the second oncovirus to have been described: it causes sarcoma in chickens. As with all retroviruses, it reverse transcribes its RNA genome into cDNA before integration into the host DNA. The RNA genome of RSV contains an extremely long 3' UTR that ranges between 5-7 kb in length which would usually direct it toward nonsense mediated decay (NMD) within the eukaryotic host cell. A conserved secondary structure element has been identified within the 3'UTR and is known as the Rous Sarcoma Virus Stability Element (RSE).[7] This element has been shown to prevent the degradation of the unspliced viral RNA.

The src gene is oncogenic as it triggers uncontrolled growth in abnormal host cells.
It was the first retroviral oncogene to be discovered. It is an acquired gene, found to be present throughout the animal kingdom with high levels of conservation between species.

The src gene was taken up by RSV and incorporated into its genome conferring it with the advantage of being able to stimulate uncontrolled mitosis of host cells, providing abundant cells for fresh infection.

The src gene is not essential for RSV proliferation but it greatly increases virulence when present.

Gag proteins (encodes capsid proteins) are necessary for virion assembly and mature virus infection of the host cell. The gag protein (Pr76) for RSV contains 701 amino acids. It is cleaved by virus encoded protease, releasing products found in the infectious virion. These cleaved products include the matrix (MA), capsid (CA), and nucleocapsid (NC), which are able to enter other pathways to infect new cells.

There are two ways viruses can enter the host cell: cell receptor endocytosis or fusion.
Endocytosis is the process where the virus binds a receptor on the target cell membrane, and the virus is taken into or endocytosed into the cell. Endocytosis can either be pH independent or pH dependent. Fusion occurs when the virus fuses together with the target cell membrane and releases its genome into the cell. RSV enters the host cell through fusion of the host cell membrane.

In order for the RSV genome transcription to occur, a primer is required.
4S RNA is the primer for RSV and 70S RNA serves as the template for DNA synthesis.
DNA polymerase or Reverse transcriptase transcribes viral RNA into the full length DNA complement.

The discovery of Rous sarcoma virus, which was reported by Peyton Rous in the Journal of Experimental Medicine (in 1911), opened the field of tumor virology. It showed that some cancers have infectious etiology, led to the discovery of oncogenes, and laid the foundation for the molecular mechanisms of carcinogenesis. Rous spent his entire research career at The Rockefeller Institute, and he was the JEM's longest serving editor.

The importance of this finding was twofold.
First, it demonstrated clearly for the first time that a malignant tumor could be induced by infection.
Many other examples of tumor-inducing viruses in rabbits, mice, cats, and nonhuman primates eventually followed, and the first oncogenic human virus, Epstein-Barr virus, was observed in 1964. Second, RSV represented a pioneering oncogenic retrovirus for investigating the molecular mechanisms of cancer development. Studies from the late 1950s onwards, after a quantitative in vitro bioassay for RSV was devised, led to the identification of oncogenes, which were initially found in retroviruses and were later found in cells.

The src oncogene of RSV became the prototype for dozens of other transforming genes in oncogenic viruses. Oncogenes function in cell signaling from growth factors, and their receptors function through signal transduction pathways to nuclear transcription factors. For example, the myc gene was first identified in an avian myelocytoma virus and the ras gene was first identified in rat sarcoma virus long before they became associated with human malignancies. The src gene product was identified, and it was the first protein to be shown to be a tyrosine kinase.

These oncogenes provide a gain-of-function in cellular signaling, stimulating cell division and leading to malignant transformation. Not long after oncogenes were discovered, DNA tumor viruses were shown to encode proteins that sequester cell proteins and induce their loss-of-function for controlling the cell cycle. The genes encoding these cell proteins became known as tumor suppressor genes. An example is p53, a transcription factor of ?53 kD that was pulled down by immunoprecipitation of the polyoma virus SV40 protein large T. The binding of the large T protein to p53 leads to a loss of p53 transcriptional activity.

The notion of transmissibility of tumors, however, predated Rous's discovery.
In 1842, Domenico Rigoni-Stern observed that nuns in Verona rarely developed cervical cancer, compared to its frequency in married women, although the causative papilloma virus was not identified until 1983. Similarly, Jaagsiekte lung carcinoma in sheep was known to be transmissible in the nineteenth century, yet the causative agent, the Jaagsiekte retrovirus, was also only characterized in 1983.

When RSV was shown to contain an RNA genome, it became the prototype "RNA tumor virus," and after the discovery of reverse transcription, the term "retrovirus" came into use. 60 years after the discovery of RSV, the first retroviral infection in a human was reported (Achong et al, 1971). This was a foamy virus that we now know represented a primary zoonotic infection from a chimpanzee, and it is apparent that primate foamy retroviruses frequently infect exposed humans. It was not until 1980 that human T cell leukemia virus type I (HTLV-1) was found to be the first genuine human retrovirus with oncogenic properties causally associated with adult T cell lymphoma-leukemia. We currently know of four circulating human retroviruses (HTLV-1 and -2 and HIV-1 and -2); there have also been many false alarms, the most recent of which was the apparent link of a xenotropic murine-related retrovirus to human prostate cancer and to chronic fatigue syndrome (Cohen and Enserink, 2011).

Gershom Zajicek M.D,
Rous sarcoma virus (RSV) ... RSV carried an oncogene called v-src which triggered sarcoma growth.
A similar oncogene called c-src is found throughout the animal kingdom with high levels of conservation between species. This simple experiment raises a profound question. Who causes sarcoma v-src or c-src?

Let' start with v-src.
Chicken sarcoma is a viral disease which starts as an infection.
Most chicken succumb to infection before getting the tumor so that only 4% get sarcoma.
94% chicken die without a sarcoma. Does this justify to call v-src an oncogene?
Oncogene is a gene that causes the transformation of normal cells into cancerous tumor cells, especially a viral gene that transforms a host cell into a tumor cell. In most infected chicken v-src fails its mission. This theoretical problem is even more pronounced in poultry leucosis. Latency poses another theoretical problem. It is the time until an infected chicken gets cancer.

Rous' discovery was also the birth of a misnomer "oncogenic virus".
Let's remember that RSV is first of all an infectious virus which in 4% causes also a sarcoma.
Obviously, the only aim of the virus is to infect. It hijacks the cell to produce virions which is also the cell's demise. Sarcoma is only a byproduct of virus-cell encounter. One wonders, what biological advantage does RSV gain by causing a sarcoma? The tumor does not produce any virions. The aim of the invading virus is to penetrate the cell, hijack its proliferation machinery, to produce virions which destroy the host (lysis). In order to protect itself the cell incorporates virus DNA into its own (lysogeny). The incorporated gene protects the host against similar viruses.

According to M. Bishop the culprit is c-src, a normal cellular gene which may cause a tumor, v-src vas originally a c-src which was hijacked by the virus and turned into v-src. Let's return to poultry infection. 96% died during lysis. 4% maintained lysogeny with the virus, grew a tumor and for a while, remained alive.
Which summarizes the essence of my hypothesis Tumor protects against virus.

Today, we tend to regard retroviral infections as being ubiquitous among vertebrate species.
While this may be the case with endogenous retroviral genomes that are transmitted as Mendelian genes in the host, not all well-studied species harbor known retroviral pathogens. It is curious that no infectious retroviruses have been identified in dogs, whereas cats harbor leukemia viruses, immunodeficiency viruses, and foamy viruses.

Today, we appreciate that ~20% of the global burden of human cancer has an infectious etiology for which preventive measures such as vaccines have great promise.

Virus: Adenovirus. DNA (MAV-1, MAD-1&2, FAV-1 to 8, TAV-1 & 2) INDEX
http://dora.missouri.edu/mouse/mouse-adenovirus-mav/ (2013)

LINK 2: http://www.zoologix.com/.../HumanAdenoviruses.htm (2015)
LINK 3: http://www.zoologix.com/.../MouseAdenoviruses.htm (2015)
LINK 4: http://emedicine.medscape.com/../300455-overview (2015-01-13)
LINK 5: http://www.criver.com/../infectious-agents/..mouse_adenovirus.aspx
LINK 6: http://avianmedicine.net/content/uploads/2013/03/32.pdf (2013)
LINK 7: https://en.wikipedia.../Coxsackie_virus_and_adenovirus_receptor (2015-08)

The Adenoviridae family consists of two genera: Mastadenovirus (contains mammalian strains) and Aviadenovirus. The two genera have a distinct group antigen. Most mastadenovirus strains have hemagglutination activity; most aviadenovirus strains do not. Aviadenovirus are divided into three groups according to common group antigens as detected by virus neutralization, growth in cell culture and nucleic acid characteristics.

Aviadenovirus are distributed around the world, and many avian species of all age groups are known to be susceptible. Because the isolation of previously uncharacterized aviadenovirus is to be expected, it is likely that the current host range is incomplete.

Adenoviruses are enveloped DNA viruses.
They contain about 36 kb of double-stranded DNA. After entry into the nucleus, genes from the early region 1 (E1a and E1b) are quickly transcribed (Fig. 1-3). During the early phase of viral replication, four noncontiguous regions of the genome are expressed (E1 to E4). They serve in part as master transcriptional regulators, starting the process of viral gene expression leading to genome replication. After the onset of DNA replication, the major late promoter drives much of the viral transcription.

Viral-encoded functions can be separated into cis and trans elements.
Whereas the cis genes, such as those responsible for the origin of replication or the packaging signal that condenses the DNA (protein IX,), must generally be carried by the virus itself, the trans genes can be complemented or replaced by inserted "foreign" DNA.

Adenoviruses are enveloped DNA viruses that cause a wide spectrum of clinical illnesses depending on the serotype of the infecting agent. These include asymptomatic illness, conjunctivitis, febrile upper respiratory disease, pneumonia, gastrointestinal illness, hemorrhagic cystitis, rash, and neurologic disease. Pneumonia is less common in adults outside of military recruit camps and similar facilities, but fulminant disease has been described in infants and in the immunocompromised population and can occur in apparently healthy hosts.

Although 52 serotypes exist, classified into 7 subgroups or species (A-G), pulmonary disease is predominantly caused by serotypes 1, 2, 3, 4, 5, 7, 14, and 21. Type 7 viruses can cause bronchiolitis and pneumonia in infants. Types 4 and 7 viruses are responsible for outbreaks of respiratory disease in military recruits.

Adenovirus serotype 14 (subgroup B) is a more virulent strain that has been reported to cause severe respiratory illness and pneumonia. Emergence of this strain was reported in 2005 among 8 of 26 civilian and military populations, with outbreaks occurring subsequently at military training centers throughout the United States.

In 2007, adenovirus serotype 14 caused a large, sustained outbreak of febrile respiratory illness among military trainees in Texas and, more recently, in a residential care facility in Washington State. In a community outbreak in Oregon, the median age was 52 years, and 76% required hospitalization, 47% required critical care, 24% required vasopressors, and 18% died. The majority of these patients were otherwise immunocompetent adults.

Spread of adenovirus is by respiratory secretions, infectious aerosols, feces, and fomites.
Neonates may acquire infection from exposure to cervical secretions at birth.

Contaminated environmental surfaces can harbor virus capable of causing infection for weeks.
The virus is resistant to lipid disinfectants but is inactivated by heat, formaldehyde, and bleach.

Adenoviruses are extremely contagious.
Studies of new military recruits have shown seroconversion rates of 34-97% over a 6-week period.
The majority of children have serologic evidence of prior adenovirus infection by the age of 10.

Adenovirus accounts for 10% of pneumonias in children.
Disease from adenovirus can occur at any time of the year.
Various adenovirus serotypes are responsible for essentially continuous epidemics of acute respiratory disease at military recruit training facilities in the United States and worldwide.

During the prevaccination era, up to 20% of recruits had to be removed from duty due to illness.
... the vaccine against adenovirus is no longer available for administration to military personnel.

Adenovirus infection has been associated with low mortality in healthy adults, but death from a 2009 community outbreak of serotype 14 pneumonia was 18%. In immunocompromised patients, adenovirus can be acquired not only by person-to-person transmission but also from reactivation, to produce a wide variety of syndromes, including gastroenteritis, hepatitis, and hemorrhagic cystitis (in addition to pneumonia), with mortality rates ranging from 38-100% and with a cumulative mortality rate of 56% in HSCT patients.

Adenoviral vectors allow for transmission of their genes to the host nucleus but do not insert them into the host chromosome. Therefore, there is a low probability of disturbance of vital cellular genes or processes. On the other hand, the adenoviral-vector approach limits gene therapy to treatment strategies in which only temporary protein expression is needed. Because the viral DNA eventually disappears, treatments for chronic conditions, such as cystic fibrosis, would have to be repeated at specific intervals. However, if only short-term activity of a gene is needed -- for example, to arouse the immune system against cancer cells or induce apoptotic stimuli -- such nonintegrating delivery vehicles are desirable.

In preclinical settings, it has been shown that adenoviral vector DNA is expressed in liver, skeletal muscle, heart, brain, lung, pancreas, and tumor tissue. When adenoviral vectors are given intravenously, most of the virus accumulates in the liver. Treatment close to reproductive organs, such as treatment for prostate and cervical cancer, has been shown to be safe. Even with replication-competent adenoviral vectors, which persist longer in the target tissue and liver, no offspring have shown germline transmission.

Adenovirus particles are 70 to 90 nm, nonenveloped and contain double-stranded DNA.
Virions are icosahedral and are composed of 252 capsomeres arranged in triangular facets with six capsomeres along each edge. There are 240 nonvertex capsomeres (hexons) and 12 vertex capsomeres (penton bases). The latter contain projections (called fibers). Members of Aviadenovirus group III contain one fiber and group I has two fibers (one long and one small). There appears to be a relative relationship between the length of the fibers and the antigenicity of the virus.

Adenovirus replicates in the nucleus producing basophilic intranuclear inclusions.
The strains have been divided into two subgroups, A and B, on the basis of their cytopathogenicity (the same as with human strains):

Subgroup A (e.g., FAV 1, FAV 2, FAV 4, FAV 5, FAV 8);
Subgroup B (e.g., FAV 5, FAV 6, FAV 7, FAV 9, Turkey [TAV] 1, TAV 2,).

MAV-1 (Mouse Adenovirus) has similarities to human adenoviruses in structure, genome organization, and some aspects of pathogenesis. Both MAV-1 and human adenoviruses cause acute and persistent infections with high morbidity and mortality in immunocompromised hosts. Respiratory infection by both mouse and human adenoviruses results in chemokine upregulation. MAV-1 primarily infects endothelial cells, which is only rarely seen for human adenoviruses.

The endotheliotropism is particularly marked in the brain, spinal cord, and spleen, and MAV-1 causes hemorrhagic encephalomyelitis accompanied by breakdown of the blood-brain barrier and altered expression of tight junction proteins. In addition, MAV-1 targets monocytes and macrophages, which are also effectors of the host response to MAV-1 infection.

Mouse adenoviruses are nonenveloped DNA viruses of the Mastadenovirus family.
There are two strains, group 1 (MAD-1) and group 2 (MAD-2).
These viruses infect both mice and rats.
These viruses survive well in the environment and can infect both humans and animals.

In humans, more than 50 serotypes of adenovirus have been identified.
Human adenoviruses commonly infect the respiratory and GI tracts, the eye, and various other tissues.
Most infections are asymptomatic, but long-term persistent infections are possible, and are a major concern to immunocompromised patients. Adenoviruses are known to be oncogenic in rodents but not in humans. They can be transmitted via direct inoculation to the conjunctiva, the fecal-oral route, aerosolized droplets, or through exposure to infected tissue or blood.

Adenovirus type 14 (Ad 14), a new variant in the United States, has been documented to cause severe and sometimes fatal acute respiratory illness in patients of all ages but especially the young, the old, patients with underlying comorbid conditions, and those who are immunocompromised.

MAdV-1 is transmitted through contact with infected urine.
Mice that recover from acute infection shed MAdV-1 in the urine for prolonged periods (1-2 years) and viral DNA persists in brain, spleen and kidney for 1 year after experimental infection. Immunodeficient mice infected with MAdV-1 may also shed virus via fecal route. MAdV-2 is shed in feces; the virus is transmitted via the fecal-oral route.

MAdV-1 infects cells of the macrophage lineage, renal tubular cells and vascular endothelial cells.
In neonatal mice, necrosis from viral replication occurs in liver, spleen, kidney, brain and adrenal gland. Intranuclear inclusions are associated with foci of necrosis and can be found in most all tissues. In susceptible adult immunocompetent mice, hemorrhagic foci occur in the brain, especially the white matter, and are associated with viral induced-damage to endothelial cells. Inclusions are uncommonly seen in brain lesions. Immunocompromised mice infected with MAdV-1 may display segmental hemorrhage in the mid small intestine; inclusions are not commonly observed.

Infection with these viruses does not cause clinical disease in adult rodents, and there are no pathologic lesions associated with infections of MAD-1 in adult mice. However, MAD-1 infection can produce a lethal disease in newborn or suckling mice characterized by infectious virus and viral lesions in multiple organs. Viral inclusions in intestinal mucosa are associated with MAD-2 infections.

Infection of mice or rats with adenoviruses can alter their normal immune response and thereby skew experimental data. For example, infection with MAD-1 can produce extensive persistent lesions in the kidneys of adult mice and render them more susceptible to experimental Escherichia coli-induced pyelonephritis. Mouse adenovirus infection has also been shown to accelerate experimental scrapie infection in mice. Although mouse adenoviral infection is usually subclinical in immunocompetent mice, wasting may result in nude mice.

Serological detection may not be useful because many mice and rats may have prior exposure to these viruses. Serological diagnosis of adenoviral infection may not be suitable because of anti-adenovirus antibodies resulting from previous exposures. Hemagglutination methodology is also not suitable for mouse adenovirus detection because these viruses simply will not hemagglutinate. Molecular detection of adenoviruses is rapid, specific and sensitive to detect the presence of the viruses. MAV infections can be confirmed by the detection of circulating antibodies. Virus can be amplified from infected tissues by PCR or cultivated in permissive cell lines. The enteric inclusions of MAdV-2 infection are pathognomonic for this agent.

Transmission (in birds) is known to occur through the oral route, and inhalation is suspected.
The virus is excreted mainly in the feces. Latently infected birds experience cyclic changes of the amount of humoral antibodies and virus titers and vice versa. Egg transmission plays a role in the maintenance of infections in a flock. A breeder hen may pass either virus or antibodies to the egg. The primary change in infected eggs is reduced hatchability.

Virulence of infestion is highly variable and poorly understood.
in addition to intrinsic damage caused by virus replication in the cells, the structural proteins of the pentons are thought to be directly toxic to host cells. During the lytic cycle of many adenoviral infections, host synthesis of macromolecules (cellular DNA, various proteins, mRNA) stops causing the host cells to die.

Aviadenovirus is generally considered to be an opportunistic pathogen.
Identified triggering factors in chickens include immunosuppression caused by infectious bursal disease and the chicken anemia virus. Reoviridae have been implicated as factors in nondomesticated avian species. Some highly virulent strains of aviadenovirus are capable of producing disease alone (hydropericardium syndrome). Aviadenovirus can trigger secondary infections by inducing mild histopathologic lesions without clinical signs. Common microscopic lesions are degeneration of hepatocytes, enterocytes and respiratory epithelial cells. These lesions allow secondary bacteria, fungi and protozoa to enter the host. Parvoviruses that require an adenovirus for replication have decreased in vitro growth and pathogenicity.

Many avian species are known or are suspected to harbor adenovirus.
A large number of strains have not been typed and in many instances, the etiologic importance of the virus is unknown. Group I strains have been associated with respiratory signs, anemia, inclusion body hepatitis, intestinal disease, pancreatitis and nephropathies. Histopathologic lesions without clinical signs are also common. The majority of aviadenovirus infections may be latent and subclinical. In other cases, adenoviruses have been isolated or detected by inclusion bodies or electron microscopy from birds with CNS signs.

Gross lesions are nonspecific including tracheitis, swelling of the liver or kidneys and catarrhal enteritis. Histopathology reveals mononuclear cellular infiltrates in the lamina propria of the trachea, hypertrophy of the mucosal glands and finally loss of the epithelium. Liver lesions vary with the virulence of the strain, but may include vacuolated degeneration of the hepatocytic cytoplasm with lymphocytic infiltration in Glisson's triangles. In more severe cases, hepatocytes show intranuclear eosinophilic inclusions, which increase in size and become basophilic before developing a halo around the inclusion. In the pancreas, irregular necrosis, mainly of the exogenic cells, with and without intranuclear inclusions, has been described. It should be emphasized that in avian species, inflammatory lesions generally develop more slowly than in mammals, and in many cases death occurs prior to inflammation so that hepatitis and enteritis may not occur.

A definitive diagnosis based on clinical or pathologic changes is not possible.
Virus isolation is best achieved from the feces, pharynx, kidneys and liver. ...
There are many indicators reported for Adenovirus' infections across a wide range of bird species, including these

... necrotic pancreatitis, ... Intracerebral infections induce clonic-tonic type CNS signs. ... sudden death or signs of respiratory disease, such as tracheal rales, coughing, ballooning skin over the infraorbital sinus, sneezing, increased lacrimation and conjunctivitis ... pulmonary edema ... Hepatic necrosis ... anorexia, a "crouching position" for one to two days, ruffled plumage, ... vomiting and respiratory distress.

At necropsy, affected birds had hepatomegaly and splenomegaly, with the former being friable and mottled. ... hemorrhagic enteritis ... Diarrhea and lethargy ... club-shaped, damaged villi in the duodenum and jejunum ... Intranuclear inclusion bodies containing adeno-like virus particles (basophilic and in part eosinophilic) may be seen ... Lymphocytic, heterophilic infiltrates occur in the intestine, liver and other parenchymatous organs.

.. The brain showed neuronal necrosis, satellitosis and proliferation of glial cells. ... enlargement of the .. duodenum. Acute necrotizing pancreatitis with large basophilic intranuclear inclusion bodies in the .. The endothelial cells of the conjunctiva and renal epithelium contained inclusion bodies suggestive of adenovirus. Inclusions in the renal tubules ... Adenovirus-like particles have been connected with acute onsets of mild diarrhea and lethargy ...

Birds that were able to maintain sufficient orientation to eat and drink usually survived. ... Tracheitis (diphtheroid) accompanied in some cases by bronchitis and pneumonia ... Grossly, (in MSD, Marble Spleen Disease) the spleen may be enlarged two to three times its normal size and is frequently mottled with multiple, grayish, confluent foci. The lung may be congested, edematous and in rare cases, hemorrhagic. ... with intranuclear inclusion bodies in RES cells (also in liver, lung and proventriculus). Extensive deposits of a slightly fibrinous material (moderately PAS-positive) may be present. These deposits are considered to be amyloid. Multiple small foci of necrosis may be present in epithelial and endothelial cells in the lungs ...

.. Adenovirus antibodies were demonstrated in flocks of guineafowl laying soft-shelled eggs. ... The lumen of the intestines may be filled with a brownish, liquid material. Histopathology reveals multifocal fibrinoid necrosis, destruction of lymphocytes and reticular cells with basophilic or eosinophilic inclusions within the nuclei of RES cells.

The presence of antibodies indicates that an infection has occurred but does not indicate what part, if any, an Aviadenovirus may have played in a disease process. Histopathology, together with in situ hybridization, electron microscopy or virus isolation are necessary for this differentiation. With the number of adenovirus serotypes, a monovalent vaccine would be of questionable value. Vertical transmission and the continuous cycle of viremia followed by antibody production in infected birds makes it exceedingly difficult to produce uninfected offspring.

Coxsackievirus and adenovirus receptor (CAR) is a protein that in humans is encoded by the CXADR gene. Human CAR protein has a theoretical molecular weight of 40.0 kDa and is composed of 365 amino acids. The human CAR gene (CXADR) is found on chromosome 21. The protein encoded by this gene is a type I membrane receptor for group B coxsackie viruses and subgroup C adenoviruses. CAR protein is expressed in several tissues, including heart, brain, and, more generally, epithelial and endothelial cells. In cardiac muscle, CAR is localized to intercalated disc structures, which electrically and mechanically couple adjacent cardiomyocytes. CAR plays an important role in the pathogenesis of myocarditis, dilated cardiomyopathy, and in arrhythmia susceptibility following myocardial infarction or myocardial ischemia.

CAR is a receptor for both Coxsackie B virus and adenovirus 2 and 5, which are structurally distinct. CAR is essential for normal development of cardiomyocytes. The expression of CAR is high in developing tissues, including the heart and brain; postnatally it is expressed in epithelial cells and in adult cardiac muscle, it is localized at intercalated discs. CAR expression is not found in normal or tumor cell lines. Expression of CAR in endothelial cells can be regulated by treatment with drugs.

Knocking out CAR is embryonic lethal by day 11.5, coordinate with severe cardiac muscle abnormalities including left ventricular hyperplasia, sinuatrial valve abnormalities, pericardial edema, thoracic hemmorhaging, myocardial wall degeneration, regional apoptosis, reduced density and disorganization of myofibrils, and enlarged mitochondria. Cardiomyocyte-specific deletion of CAR after embryonic day 11 had no noticeable effect on development and postnatal life, suggesting that CAR is critical during a temporal window of cardiac development.

Studies from human hearts have shown that lower expression of CXADR mRNA is associated with a risk allele at chromosome 21q21, which may in fact predispose hearts to arrhythmias. To discern the mechanistic underpinnings, hearts from heterozygous CAR knockout mice subjected to acute myocardial ischemia were evaluated and showed slowed ventricular conduction, earlier onset of ventricular arrhythmias, and increased susceptibility to arrhythmias. These findings were coordinate with a reduction in magnitude of the sodium current at intercalated discs ...

CAR is strongly expressed in the developing central nervous system where it is thought to mediate neurite outgrowth. In contrast,expression of CAR is undetectable in the adult nervous system. It functions as a homophilic and heterophilic cell adhesion molecule through its interactions with extracellular matrix glycoproteins such as: fibronectin, agrin, laminin-1 and tenascin-R. In addition, it is thought to regulate the cytoskeleton through interactions with actin and microtubules. Moreover, its cytoplasmic domain contains putative phosphorylation sites and a PDZ-interaction motif which suggests a scaffolding role. It has also been shown that CAR is critical for the development of lymphatic vasculature and in forming lymphatic endothelial cell-cell junctions.

In patients with myocarditis or dilated cardiomyopathy, elevated Coxsackie B2 viral nucleic acids have been detected in myocardial biopsy samples. Adenoviral genomic DNA has also been detected in myocardial biopsies of patients with idiopathic cardiomyopathy, or impaired left ventricular function of unknown origin. Patients exhibiting sudden death from acute myocardial infarction had a higher proportion of active coxsackie B virus infection relative to matched controls, which was coordinate with disrupted sarcolemmal localization of dystrophin, suggesting that enteroviral infection may worsen the outcome of patients with acute myocardial infarction.

A role for CAR in arrhythmia susceptibility and ventricular fibrillation after myocardial infarction was shown in that CXADR lies near the 21q21 locus, which is strongly associated with these insults.

February 2, 2006
Madison, WI - The fast spread of what the World Health Organization calls a "global epidemic of obesity" is wreaking havoc on human joints, especially knees. New research on human adenoviruses suggests that the rise in global fat might be due in part to virally induced changes in adipose cells.

Dr Leah D Whigham (University of Wisconsin, Madison) and colleagues have identified a third human adenovirus that increases fat and decreases lean body mass in animal models.

"With the exception of infectious diseases, no other chronic disease in history has spread so rapidly [as obesity has], and the etiological factors producing this epidemic have not been clearly identified," Whigham writes in a paper published in the January 2006 issue of the American Journal of Physiology: Regulatory, Integrative and Comparative Physiology.

Senior author Dr Robert L Atkinson (Obetech Obesity Research Center, Richmond, VA) found in previous studies that human adenovirus-36 (Ad-36) increases adiposity in chickens, mice, and nonhuman primates and that exposure to Ad-36 is associated with increased body weight in humans.

Atkinson found antibodies to Ad-36 in 30% of obese subjects vs 11% of nonobese subjects (p<0.001)>. The association was independent of age and gender. Atkinson also found that in twin pairs discordant for the Ad-36 antibody, the Ad-36-positive twin had higher body-mass index (BMI 24.5 vs 23.1, p<0.03) and more body fat (29.6% vs 27.5%, p<0.04) [ 3 ].

Whigham reports that adenovirus-37 (Ad-37) also has fat-promoting properties.
Animals inoculated with Ad-37 had significantly higher visceral fat and total body fat than animals in comparator groups (p<0.001)>, despite having the same food intake. The Ad-37 animals also had higher serum cholesterol levels but reduced triglycerides.

Both Ad-36 and Ad-37 appear to work directly on cells by increasing the differentiation of preadipocytes to adipocytes, apparently through insertion of the viral gene E40rf1. Mean final body weights of the Ad-37 animals in Whigham's study did not differ from weights of control animals, but they showed a major shift from lean to fat.

"The Ad-37 group had almost threefold more visceral fat and over twofold more total body fat vs the control group," Whigham writes. ...

Gene Therapy.
Adenoviruses are among the most commonly used vectors for gene therapy, second only to retroviruses.

The adenoviruses have several features that make them well suited for use in gene therapy.

First, they are ubiquitous: adenoviruses have been isolated from a large number of different species, and more than 100 different serotypes have been reported, some 43 in humans. Most adults have been exposed to the adenovirus serotypes most commonly used in gene therapy (serotypes 2 and 5).

Second, adenoviral vectors rapidly infect a broad range of human cells and tend to yield high levels of gene transfer compared to levels achieved with other currently available vectors.

Third, adenoviral vectors have low pathogenicity in humans: they cause few and only mild symptoms associated with the common cold.

Fourth, adenoviral vectors can accommodate relatively large segments of DNA (up to 7.5 kilobase pairs [kb]) and transduce these transgenes in nonproliferating cells.

Fifth, the viral genome does not undergo rearrangement at a high rate, and inserted foreign genes are generally maintained without change through successive rounds of viral replication.

Finally, adenoviral vectors are relatively easy to manipulate using recombinant DNA techniques.

Virus: Cytomegalovirus. (CMV, MCMV, HHV-5, HCMV) INDEX
https://en.wikipedia.org/wiki/Cytomegalovirus

LINK 2: http://www.zoologix.com/.../MouseCytomegalovirus.htm
LINK 3: http://emedicine.medscape.com/../300455-overview (2015-01-13)
LINK 4: http://www.healthgrades.com/conditions/cytomegalovirus
LINK 5: http://viralzone.expasy.org/all_by_species/180.html
LINK 6: http://www.mayoclinic.org/../cmv/../con-20029514 -- 2014-04
LINK 7: https://www.nlm.nih.gov/medlineplus/.../000568.htm -- 2015-09
LINK 8: http://www.scielo.cl/.../v138n10/art%2016.pdf (2010-10)
LINK 9: http://www.cdc.gov/cmv/overview.html

Cytomegalovirus (CMV) is a genus of viruses in the order Herpesvirales, in the family Herpesviridae, in the subfamily Betaherpesvirinae. Human and monkeys serve as natural hosts. There are currently 8 species in this genus including the type species human herpesvirus 5. Diseases associated with HHV-5 include mononucleosis, and pneumonias.

The species that infects humans is commonly known as human CMV (HCMV) or human herpesvirus-5 (HHV-5), and is the most studied of all cytomegaloviruses. Within Herpesviridae, CMV belongs to the Betaherpesvirinae subfamily, which also includes the genera Muromegalovirus and Roseolovirus (HHV-6 and HHV-7). It is related to other herpesviruses within the subfamilies of Alphaherpesvirinae that includes herpes simplex viruses (HSV)-1 and -2 and varicella-zoster virus (VZV), and the Gammaherpesvirinae subfamily that includes Epstein-Barr virus (EBV).

All herpesviruses share a characteristic ability to remain latent within the body over long periods. Although they may be found throughout the body, CMV infections are frequently associated with the salivary glands in humans and other mammals. Other CMV viruses are found in several mammal species, but species isolated from animals differ from HCMV in terms of genomic structure, and have not been reported to cause human disease.

CMV pneumonia is considered the most common life-threatening complication of bone marrow transplantation (BMT) and solid-organ transplantation.

The rate of CMV pneumonia in BMT (bone marrow transplant) recipients is 10-50%, as reported in different studies. In patients receiving solid-organ transplants, CMV reactivation is reported in as many 70% of patients, but only 20% develop clinically significant infections. Studies of CMV pneumonia in BMT recipients demonstrate a 31% mortality rate in treated patients and a decrease from previously reported rates of 56-100% in untreated patients. The mortality rate is reportedly 75% in untreated immunosuppressed persons.

Cytomegalovirus (CMV) is a common virus that can infect almost anyone.
Most people don't know they have CMV because it rarely causes symptoms.
However, if you're pregnant or have a weakened immune system, CMV is cause for concern.
Most CMV infections are not diagnosed because CMV usually causes few, if any, symptoms.
Among every 100 adults in the United States, 50-80 are infected with CMV by the time they are 40 years old. A blood test ( CMV DNA serum PCR test) can tell whether a person has ever been infected with CMV.

Cytomegalovirus is related to the viruses that cause chickenpox, herpes simplex and mononucleosis.
Once you're infected with CMV, the virus remains with you for life, but it's not always active. CMV may cycle through periods during which it lies dormant and then reactivates. If you're healthy, it mainly stays dormant. You can pass the virus to others during reactivation.

CMV spreads from person to person through body fluids, such as blood, saliva, urine, semen and breast milk. CMV spread through breast milk usually doesn't make the baby sick. However, if you are pregnant and develop an active infection, you can pass the virus to your baby.

There's no cure for CMV, but drugs can help treat newborns and people with weak immune systems.

Pregnant women who become infected are at low risk of transmitting the virus to their babies.
If it's the first time you've had the infection (primary CMV), risk of transmitting the virus to the baby is higher than it is with reactivated infection. Transmission usually occurs during the first half of pregnancy, usually the first trimester.

Most babies who are infected before they're born appear healthy at birth, but a few develop signs over time -- sometimes not for months or years after birth. The most common of these late-occurring signs is hearing loss. A small number may develop vision impairment as well.

Babies with congenital CMV who are sick at birth tend to be very sick.

Signs and symptoms include:
• Yellow skin and eyes (jaundice)
  Eye abnormalities, including central vision loss, scarring of the retina, an inflammation of the light-sensing layer of the eye (retinitis), and swelling and irritation of the eye (uveitis).

• Purple skin splotches or a rash or both
• Small size at birth (or low birth weight) -- Small head
• Lack of coordination
• Hearing loss
• Enlarged spleen
• Enlarged and poorly functioning liver
• Pneumonia
• Seizures
• Death

An illness resembling infectious mononucleosis is the most common presentation of CMV in people with weakened immune systems (immunocompromised). CMV also can attack specific organs.

Signs and symptoms may include:
• Fever
• Pneumonia
• Diarrhea
• Ulcers in the digestive tract, possible causing bleeding
• Hepatitis
• Inflammation of the brain (encephalitis)
• Behavioral changes
• Seizures
• Coma
• Visual impairment and blindness

Less common symptoms include:

• Chest pain
• Cough
• Headache
• Hives
• Irregular heartbeat
• Jaundice
• Neck stiffness
• Rapid heart rate
• Sensitivity to light
• Shortness of breath
• Swollen spleen and liver

Most people infected with CMV who are otherwise healthy experience few if any symptoms.
When first infected, some adults may have symptoms similar to mononucleosis, including fatigue, fever and muscle aches. CMV infection in people with compromised immunity can be fatal.

CMV mononucleosis.
This syndrome resembles infectious mononucleosis, but the Epstein-Barr virus (EBV) causes classic mononucleosis. If you have signs and symptoms that resemble mononucleosis -- a sore throat, swollen glands and tonsils, fatigue, and nausea -- your doctor will test you for the antibody your body makes to fight off EBV. If it's absent, there's a chance CMV is causing your symptoms.

Intestinal complications.
CMV infection in your intestines can result in diarrhea, fever and abdominal pain; inflammation of your colon; and blood in your stool.

Liver complications.
CMV can cause abnormal functioning of your liver and an unexplained fever.

Nervous system complications.
A variety of neurological complications have been reported as a result of CMV infection in the nervous system. These may include inflammation of your brain (encephalitis).

Lung complications.
CMV can cause inflammation of your lung tissue (pneumonitis).

Most patients recover in 4 to 6 weeks without medication.
Rest is needed, sometimes for a month or longer to regain full activity levels.
Painkillers and warm salt-water gargles can help relieve symptoms.

Cytomegalovirus (CMV) is a herpesvirus that is a common cause of infections, usually asymptomatic, in the general population. In hosts who are immunocompetent, acute CMV infection causes a mononucleosis-like syndrome. Transmission is primarily through body fluid contact. The virus has been found in the cervix and in human milk, semen, and blood products. The prevalence of antibodies to CMV in adults ranges from 40-100%, with higher rates in lower socioeconomic areas.

Reactivation of latent infection is almost universal in transplant recipients and individuals infected with the human immunodeficiency virus (HIV). CMV pneumonia may occur and is often fatal in immunocompromised individuals, primarily hematopoietic stem cell transplant (HSCT) and solid organ transplant (SOT) recipients. The severity of pneumonia is related to the intensity of immunosuppression. Additionally, CMV infection is itself immunosuppressive, causing further immunocompromise in these patients.

In cancer patients receiving allogeneic bone marrow transplants, CMV pneumonia has a prevalence of 15% and a mortality rate of 85%, making it the most common cause of death in this population. Acute graft-versus-host disease is the major risk factor for CMV pneumonia in these patients.

Interestingly, although CMV is a well-recognized pathogen in patients with AIDS (manifesting as retinitis, colitis, encephalitis, polyradiculitis, and/or cholangiopathy), clinically relevant pneumonia is very uncommon in this group, even if CMV is cultured from alveolar fluid and/or seen on lung histology.

Viral replication is nuclear, and is lysogenic.
Entry into the host cell is achieved by attachment of the viral glycoproteins to host receptors, which mediates endocytosis. Replication follows the dsDNA bidirectional replication model. DNA templated transcription, with some alternative splicing mechanism is the method of transcription. Translation takes place by leaky scanning. The virus exits the host cell by nuclear egress, and budding. Human and monkeys serve as the natural host. Transmission routes are contact, urine, and saliva.

The CMV promoter is commonly included in vectors used in genetic engineering work conducted in mammalian cells, as it is a strong promoter and drives constitutive expression of genes under its control.

Mouse cytomegalovirus (MCMV) is a member of the beta herpes virus family and is a large, double stranded DNA virus with a genome size of approx 230 kb. Similarly to rat CMV, two strains of MCMV have been described: MCMV1, and more recently MCMV2 (Teterinal et al., 2009).

MCMV has broad tissue tropism, and can infect the host's epithelial cells such as salivary gland tissue, as well as macrophages and lymphoid cells. In natural infections, no clinical symptoms may be detected. The submandibular salivary gland is the primary site of lesions; other salivary glands are rarely involved. A substantial percentage of infected mice may eventually develop latent infections, and the virus may be transmitted to other mice through biting.

Wild mice remain the reservoir for the virus.
Approximately 90% of wild mice are infected with MCMV.

Virus: Encephalomyocarditis -- RNA. (EMCV, TBEV) INDEX
https://en.wikipedia.org/wiki/Cardiovirus_A (2015-03)

LINK 2: http://www.zoologix.com/rodent/Datasheets/Encephalomyocarditis.htm (2015)
LINK 3: https://en.wikivet.net/Encephalomyocarditis_Virus (2013-10)
LINK 4: http://encyclopedia2.thefreedictionary.com/encephalomyocarditis+virus (2015)
LINK 5: http://www.thepigsite.com/.../138/encephalomyocarditis-virus-emcv/ (2014)

Encephalomyocarditis virus (EMCV) is a single stranded RNA (ssRNA) virus that causes encephalomyocarditis in pigs. It is a cardiovirus from the family Picornaviridae, and like other picornaviruses it is stable over a wide range of pH. The virus is ether-resistant and can be inactivated at 60°C for 30 minutes, although some are more thermally stable. Infection with the virus causes encephalomyocarditis and reproductive disease in pigs. Although a variety of mammals may host the virus, pigs are classed as the domestic host as they are most easily infected. It is thought to be spread by rodents.

The disease can be found worldwide but is of greatest economic importance in tropical areas.
One strain, type A, causes reproductive problems, a second strain, type B, causes heart failure and other strains are mild or non pathogenic. Both types A and B occur in Europe (e.g. Belgium) but in most countries of Europe, particularly those in the EU, it tends to be relatively mild or non-pathogenic and disease in pigs is rarely diagnosed. In Australia the strains appear to be much more virulent for pigs than those in New Zealand. Virulent strains in Florida, the Caribbean and probably Central America damage the heart and cause death whereas those in the Mid West of the US tend to cause reproductive problems. Clinical disease in pigs often occurs when rat numbers increase to plague levels. Pigs can be infected from rats or from rat-contaminated feed or water. It does not seem to spread very readily between pigs.

Piglets that are infected present with encephalitis, myocarditis and sudden death.
Mortality rates can be high. If a sow is infected whilst pregnant she may present with a variety of reproductive signs including infertility, mummification, abortion, still birth and the birth of weak piglets. A variety of gastrointestinal, respiratory and systemic signs may also be seen as the virus infects multiple body systems. ... the first signs are often a few miscarriages near the end of pregnancy. Then over a period of about 3 months the numbers of mummified foetuses and stillbirths increase and pre-weaning mortality rises. The farrowing rate worsens. Affected females may go through a phase of fever and lack of appetite. In affected herds there are usually no clinical signs in weaned and growing pigs.

A presumptive diagnosis can be made based on the history and clinical signs.
Clinical signs include vomiting and regurgitation, anorexia, pyrexia, fasciculations, tachypnea, dyspnea, open mouth breathing and sudden death. Neurological signs include ataxia, generalised weakness, tetraparesis, inability to stand, tremor, dysmetria, lethargy and depression. Pregnant sows that become infected can suffer from infertility, mummified fetus, abortions, still births, small litter and weak new born. Virus isolation is necessary for definitive diagnosis. Postmortem examination of piglets may or may not reveal cardiac pathology but histopathology should show cardiac and brain abnormalities. Signs in aborted fetuses are highly variable.

Encephalomyocarditis virus (EMCV) is a single stranded picornavirus belonging to the cardiovirus genus that infects many animal species including pigs, rodents, cattle, elephants, raccoons , marsupials, baboons, macaques, chimpanzees and humans. Rats and mice are the natural hosts of the virus, but pigs are the most commonly and severely infected domestic animals. The ability of this virus to cause interspecies infections had led to numerous outbreaks in zoos in Australia and the United States (Reddacliff et al., 1997; Wells and Gutter, 1989). These outbreaks involved multiple animal species including lemurs, squirrels, macaques, mandrills, chimpanzees, hippopotami, kangaroos and possibly humans.

Humans infected with this virus may have symptoms including fever, neck stiffness, lethargy, delirium, headaches, or vomiting (Gajdusek, 1955; Murname, 1981). In recent years, there has been renewed interest in this virus, especially in pig-to-human transmission, because of advances in xenotransplantation as a means of overcoming the acute shortage of transplantation tissues and organs for humans. Cardiomegaly and myocardial lesions with yellow or white necrotic foci (2-15mm diameter) are common and usually present on the epicardium of the right ventricle.

These lesions can also be characteristic of Vitamin E and selenium deficiency. Acutely affected pigs may not show any gross lesions on post mortem. Histopathological findings include myocarditis with focal or diffuse accumulation of mononuclear cells, vascular congestion, oedema, degeneration of the myocardial fibres with necrosis and occasional mineralization of necrotic heart muscle. Brain tissue can be congested with evidence of meningitis, perivascular infiltration (mononuclear cells) and neuronal degeneration.

Tick-borne encephalitis virus (TBEV) belongs to the genus Flavivirus in the family Flaviviridae. Infections can result in acute central nervous system disease in humans and animals. Three subtypes of TBEV have been reported: far eastern (FE), Siberian (Sib) and European (Eu) subtypes, which are distributed over a wide area of Europe and Asia. The tick vector of the FE and Sib subtypes is Ixodes persulcatus and that of the Eu subtype is Ixodes ricinus.

Besides transmission through tick bites, the virus can also be passed on by ingestion of unpasteurized dairy products such as milk and cheese from infected goats, sheep, or cows. Transmission through laboratory exposure, breastfeeding, blood transfusion, and contact with slaughtered viremic animals has also been reported, but these modes of transmission are rare.

Human infections can develop a biphasic course involving acute febrile illness, then a period of apparent recovery, followed by neurological symptoms including headache, meningitis, meningoencephalitis and meningoencephalomyelitis. Death can occur within 5 to 7 days from the onset of neurological signs. However, many viral infections can cause similar symptoms, so laboratory confirmation is needed.

In the past, diagnosis of EMCV was based on virus isolation and identification.
This method is time-consuming and the virus is difficult to isolate from infected animals.
Experimental EMCV infection in pigs showed that virus could no longer be isolated after 3 days post-infection (Foni et al., 1992), but the virus may continually persist for a long period in infected pigs without any clinical signs (Billinis et al., 1999). Confirmation of this pathogen has relied upon the development of circulating antibody, but this diagnostic approach is not reliable because a recent study in pigs has shown that some infected pigs may not develop antibodies against EMCV (Brewer et al., 2001).

EMCV detection by PCR is a rapid, sensitive and specific method for the diagnosis of this infection.
PCR methodology can reduce the frequency of false negative diagnoses of this virus.

Besides protecting laboratory personnel from accidental exposure to pathogenic viruses in blood samples from infected subjects, the viral inactivator (Interferon) could significantly reduce the occurrence of blood-transmitted diseases, including HIV-1, poliovirus, foot-and-mouth disease virus, influenza, encephalomyocarditis virus (a model virus for hepatitis A), bovine diarrhea virus (a model virus for hepatitis C), equine encephalitis virus, and Ebola.

Virus: Ectromelia, the DNA poxvirus of mice. (ECTV) INDEX
https://en.wikipedia.org/wiki/Ectromelia_virus

LINK 2: http://microbewiki.kenyon.edu/index.php/Ectromelia_virus (2011-12)
LINK 3: http://www.zoologix.com/rodent/Datasheets/Mousepox.htm
LINK 4: http://dora.missouri.edu/mouse/ectromelia-virus-mousepox/ (2013)

Ectromelia virus (ECTV) is a zoonotic viral disease.
It belongs to the Poxviridae family of the genus Orthopoxvirus and is among the species of Vaccinia virus. Virions are oval or brick-shaped with a dimension of approximately 175 X 290 nm. It has a linear, double-stranded DNA genome that is 209,771 bp, surrounded by a layer of lipids. This host-specialized virus infects with high efficiency, with the ability to spread systematically within its host and be effectively transmitted to others. The virus replicates in the cell cytoplasm and it encodes its own replication and transcription machinery. Members of the poxvirus family include variola virus, one of the most virulent human pathogens that caused smallpox, and vaccinia virus, the smallpox vaccine.

The interaction between the virus and the mouse is obligate pathogenesis.
It can be transmitted through direct contact with an infected animal or through fomites.
Transmission via the respiratory route has also been thought to be a possible route of entry as well.
The skin is the natural route of the infection through abrasions in the skin. The virus is then able to replicate in the epidermis layer of the skin and then spread from the release of virual progeny from the initial infected site.

Natural infections can occur via the fecal-oral route and urine contamination.
Newly infected mice may develop pustules in approximately 10 days which often resemble bite marks.
Resulting necrosis may lead to the loss of digits and limbs and destruction of liver and lymphoid tissue. Mortality is very high and can reach 100%. Many infected animals, however, may develop latent infections with no clinical symptoms which can be reactivated by stressors such as irradiation and transport. Upon necropsy an enlarged spleen and intestinal hemorrhaging are often noted.

Primary viraemia is a result of the virus' release into the bloodstream, causing infection of the spleen, liver, and other central organs. Secondary viraemia is due to the release of the virus from infected organs which results in infection of the skin. Clinical manifestations include swelling of the feet, amputation of the tail or feet, erosions, and encrustations on face, ears, feet or tail. ... Histologic lesions include massive splenic, lymph node, thymic and hepatic necrosis, small intestinal mucosal erosions, and cytoplasmic inclusions in the skin and liver.

Although clinical and gross lesions are suggestive of the disease, histological demonstration of intracytoplasmic inclusion bodies (arrowheads) in epithelial cells surrounding vesicular skin ulcers in small intestinal and pancreatic cells is helpful to confirm the diagnosis. ... In acute disease, there is high morbidity and high mortality with affected animals exhibiting hunched posture, conjunctivitis and facial swelling. Subacute to chronically infected animals develop a cutaneous vesicular body rash which often progresses to swelling, necrosis and sloughing of the extremities. Deaths are sporadic.

The incubation period for the virus is approximately 7 to 10 days.
The infected animal will then begin to shed the virus and lesions that are characteristic of the virus begin to appear at the base of the tail. Swelling from the primary infection site will also occur as an inflammatory and immune response to the invading virus. Ultimately, infection leads to death. However, depending on the strain of ECTV mice can recover from the infection after three weeks to 116 days.

Diagnosis of the disease has often been based on its distinctive lesions but this approach is not reliable because some latently-infected mice and rats may not have symptoms. Serological detection may indicate prior exposure but cannot confirm the current presence of virus in those latently-infected rodents. Molecular detection is a rapid, sensitive and specific method to detect and confirm the presence of mousepox virus.

Virus: H-1 (Toolan) virus. (THV) INDEX
http://www.usbio.net/item/209245

LINK 2: http://www.pharmacopeia.cn/v29240/usp29nf24s0_c1050s5.html
LINK 3: http://www.gv-solas.de/.../Infektionserreger/Toolan_s_H-1_Virus.pdf
LINK 4: http://www.criver.com/files/pdfs/infectious-agents/rm_ld_r_rat_parvoviruses.aspx
LINK 5: http://www.nature.com/gt/journal/v6/n3/pdf/3300832a.pdf
LINK 6: http://www.nap.edu/read/1429/chapter/15 (2015)

Animals, just like humans, are susceptible to various bacterial and viral infections.
Animals are used widely in biomedical research. Laboratory animal infections may compromise the health of the animals and ultimately the research data derived from them. Microbial infections alter not only the animal behavior but also the biological responses. Apart from the use of whole animals for experimentations, numerous animal cell lines and proteins are also derived from animals and used in biomedical research. Animals or animal-derived products are transported from one part of the world to another in a matter of days. So there is great potential for the diseases to spread very quickly.

Many infections are asymptomatic and without any overt clinical symptoms.
Detection of microbial infections has relied largely on serological screening and presence of microbial antigens or antibodies. Parvovirus casually applied to all the viruses in the Parvoviridae taxonomic family and also the taxonomic name of the Parvovirus genus within the Parvoviridae family. Parvoviruses (from Latin parvus meaning small) are typically linear, non-segmented single-stranded DNA viruses, with an average genome size of 5Kb.

Parvoviruses tend to be specific about the taxon of animal they will infect.
The genus Parvovirus presently contains 13 distinct serotypes, three of which occur in rodents: KRV, H-1 virus, and Minute Virus of Mice. The viral capsid of a parvovirus is made up of two or three proteins, known as VP1-3 that form an icosahedral structure that is resistant to acids, bases, solvents and temperature up to 50°C. Structural protein (NS1-2) are conserved and involved in transcription and virus replication. Capsid proteins (VP1-3) exhibit heterogeneity among different parvoviruses. Parvovirus diagnosis is by serology and ELISA (or enzyme-linked immunosorbent assay). MPV is most pathogenic for haematopoietic cells than mouse parvoviruses (MPVs).

Rat Toolan's H-1 (H-1/or THV) is a member of parvovirus family and closely related to the minute virus of mice (MVM). The clinical signs associated with a natural THV infection lead to cell death.

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 desiccation, pH 2 to 11, chloroform, ether, and alcohol.

Characteristics:
• natural host: laboratory and wild rats
• mouse cells cannot be infected by H-1
• hamsters and other species can be infected experimentally
• increased abortion rate
• highly temperature resistant
• no clinical signs after natural infection
• highly resistant at different pH values, desiccation and other environmental conditions
• viral replication only in mitotically active tissues like, e.g. embryo, intestines, tumours
• in various human lymphoma-derived cells a persistent infection can occur

• contaminant of permanent human cell lines
• pathogenic for the developing liver and cerebellum
• delayed healing of bone fractures and altered callus formation
• viral inclusion bodies in animals bearing larval forms of tapeworms
• inhibition of lipid formation in rat kidney cells in vitro
• infection of human cells is increased after oncogenic transformation
• H-1 together with KRV and C. piliforme can influence the prevalence rate of Yersinia-induced arthritis in rats

• presence of H-1 virus reduces the number of tumours produced by an oncogenic adenovirus in hamsters
• reduced incidence of spontaneous tumours in hamsters experimentally infected at birth
• reduced incidence of chemically induced tumours in experimentally infected hamsters
• inhibition of tumour formation in nude mice from a transplanted human tumour and retardation of tumour growth

MVM was isolated from a human tumor cell line (HEp-1) after it had been passaged in rats, and therefore, the virus was probably of rat origin. Like Kilham rat virus, H-1 virus has been used to produce experimental malformations of the central nervous system, skeleton and teeth, particularly in rats and hamsters. The natural history of H-1 virus in rat populations has been studied very little.

The epizootiological characteristics of H-1 virus infection in rat colonies are generally assumed to be similar to those of Kilham rat virus infection which has been investigated much more extensively. Transmission is primarily horizontal, and virus is shed in urine, feces, nasal secretions, and milk.

The diagnosis of H-1 infection is usually made during health surveillance testing as natural infections are inapparent. The enzyme-linked immunosorbent assay and indirect fluorescent antibody test are usually used for initial screening, followed by either the HAI, CF, or NT tests for discriminating between H-1 virus and Kilham rat virus infections.

H-1 virus has been reported to cause hepatocellular necrosis in infected rats when they are subjected to liver injury by hepatotoxic chemicals, parasitism, or partial hepatectomy. H-1 virus infection has been found to inhibit experimental tumor induction by adenovirus 12 and dimethylbenzanthracene in hamsters.

Virus: Sialodacryoadenitis coronavirus. RNA (SDAV) INDEX
http://ratguide.com/health/viruses/sda.php

LINK 2: https://en.wikivet.net/Sialodacryoadenitis_Virus (2012-07)
LINK 3: http://www.petmd.com/...sialodacryoadenitis_coronavirus (2015)
LINK 4: http://www.zoologix.com/rodent/Datasheets/RatCoronavirusSDAV.htm
LINK 5: http://dora.missouri.edu/rats/coronaviruses-rcv-and-sdav/
LINK 6: http://www.criver.com/files/pdfs/infectious-agents/.. (2009)
LINK 7: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC421307/
LINK 8: http://www.nfrs.org/sdav.html

Sialodacryoadenitis virus is an RNA virus, enveloped, genus coronavirus.
Sialo= "salivary" + dacryo = "lacrimal" + adenitis = "inflammation of lymph nodes and glands"

Most rats will show clinical signs within a few days of their first exposure to SDAV.
SDAV has a tropism for tubuloalveolar glandular tissue of serous or mucous/serous glands.
Consequently, SDAV infection results in damage to lacrimal, salivary, and Harderian glands.
In epizootic infections, animals present with sniffling, sneezing, photophobia, chromodacryorrhea, and submandibular swelling. Morbidity is high, but mortality is low.

In enzootically infected colonies, clinical signs are absent or very mild.
Sequelae to SDAV infection include megaloglobus, corneal ulceration, and hyphema secondary to the damage to the lacrimal glands. Other strains, historically referred to as rat coronavirus (RCV), have a respiratory tropism and can cause inflammation, generally mild, of the respiratory tract from the nose to the lungs. Immunodeficient rats can be persistently infected, and the infection presents with severe clinical signs and may be fatal.

Sialodacryoadenitis and rat coronavirus are inter-related viral infections that affect the nasal cavities, lungs, salivary glands and the Harderian gland that is close to the eyes in rats. These are highly infectious diseases that can be spread from rat to rat simply by being in the same vicinity as an infected rat. Aerial spread of the virus is common through sneezing by the infected rats. In addition, rats do not always show signs of being infected, making this virus an unexpected danger. An infected rat may carry the virus quietly and without symptoms for a week. These viral infections last from two to three weeks.

An infected rat's symptoms will depend on the organs that are most affected by the infection.
In fact, a rat may be a carrier of the virus for up to a week sometimes without displaying any symptoms. Discharge from the eyes along with mumps-like symptoms will be present with primary sialodacryoadenitis infection. Other symptoms that may occur include:

• Excessive sneezing
• Discharge from nose
• Enlarged salivary glands -- swelling around the neck
• Lymph nodes may be swollen in immune system response
• Mumps
• Avoidance of bright light (photophobia)
• Reddish brown pigments and discharge around the eyes
• Inflammation of cornea or conjunctiva (eye tissue)
• Squinting
• Blinking
• Eye rubbing
• Excessive scratching at eyes
• Dehydration, if loss of appetite is present
• Fluid-filled lungs

Rats typically recover over a period of two to three weeks, developing resistance to future attacks by these viruses as their immune system responds and builds natural antibodies to the virus. However, you must treat every rat for severe respiratory infections as soon as it begins to show symptoms of any type of viral infection. The preferred choice of treatment is a combination of enrofloxacin, also known as baytril, and doxycycline.

Some strains may cause an interstitial pneumonia in young rats and disease may be exacerbated by concurrent Sendai virus infection. Signs may be mimicked by Sendai virus, corona virus and secondary bacterial infection with Pasteurella pneumotropica and Mycoplasma pulmonis.

Sialodacryoadenitis is an infectious disease of rats caused by rat coronavirus (RCV).
This infection of rats has been recognised for many years but the causative agent was not discovered until 1970, when the first virus of this group was isolated. This virus was designated Parker's Rat Coronavirus (PRC) after its discoverer. A second virus, Sialodacryoadenitis virus or SDAV was discovered just two years later. These two viruses are very similar and are now considered to be strains of the same virus, namely Rat Coronavirus or RCV. Since then, several more strains have been reported, including CARS (not the same as CAR bacillus), RCV-BCMM, RCV-W and RCV-NJ. This is a virus that mutates frequently and whose virulence can vary widely, from rat to rat, strain to strain and outbreak to outbreak.

Virus: Hantavirus. RNA - (HFRS, KHF, EHF, NE) INDEX
https://en.wikipedia.org/wiki/Hantavirus
Hupei I, SR-11, Hallnas-I, Tchoupitoulas, Purimala, Prospect Hill-I, Girard Point.

LINK 2: http://emedicine.medscape.com/../300455-overview (2015-01-13)
LINK 3: http://www.zoologix.com/rodent/Datasheets/Hantavirus.htm
LINK 4: http://www.cdc.gov/hantavirus/technical/hanta/virology.html
LINK 5: http://www.auuuu.org/respiratory/hantaviruses/
LINK 6: http://www.cdc.gov/hantavirus/pdf/hps-fact-sheet.pdf
LINK 7: http://www.usbio.net/item/209245
LINK 8: http://www.nap.edu/read/1429/chapter/15 (2015)

Hantavirus is a genus of enveloped, single-stranded RNA viruses in the family Bunyaviridae.
The majority are transmitted by arthropod (insect) vectors. Hantaviruses, however, are harbored by rodents, with each viral species having one major rodent host species. Rodents, which are chronically infected, excrete hantaviruses from urine, saliva, and feces. Infection occurs after aerosols of infectious excreta are inhaled.

The hantaviruses are a group of closely related viruses that occur primarily in wild rodents but that also have been found in laboratory rats, mainly in Japan and Europe. Some of the hantaviruses cause serious zoonotic infections in people.

The genus Hantavirus includes several recently recognized viruses ...
Some of these agents have caused persistent, subclinical infections in laboratory rats (and other rodents introduced into laboratories), resulting in serious illness in research personnel. The most important human pathogen in the group, Hantaan virus, has been called "the most significant zoonotic pathogen of laboratory rodents since the discovery of lymphocytic choriomeningitis virus"

The Hantavirus pulmonary syndrome (HPS) is seen in the Americas and is an acute pneumonitis caused by the North American Hantavirus, most notably the Sin Nombre Virus. Two other agents, isolated in other parts of North America, can also cause HPS.

Hantaviruses originally were recognized in the four-corners region of the southwestern United States (New Mexico, Arizona, Utah, and Colorado) in May 1993 (Potentially bioengineered). The deer mouse (Peromyscus maniculatus) was identified to be the reservoir.

As of July 2010, 545 cases of HPS had been reported in the United States from 32 states, mostly New Mexico, Colorado, Arizona, California, Washington, Texas, and Utah (in decreasing order of prevalence). HPS is also reported in South America and in Canada. The mortality rate for HPS is 35%. Of individuals with HPS, 61% are men and 39% are women, with a mean age of 37 years. Caucasian patients account for 77%, people of Native American descent account for about 20%, and those of Hispanic descent account for 13%.

Hantavirus is a new genus based on morphological, genetic, antigenic, and physiochemical similarities.
Collectively, they have been grouped together by the World Health Organization as the viruses of hemorrhagic fever with renal syndrome (HFRS) in humans. Hantaan virus, the cause of KHF, is the prototype member of the genus. Thus far the genus has not been separated into species but several strains of hantaviruses have been isolated: Hupei-I from a patient with EHF in China; SR-11 from a laboratory rat associated with an EHF outbreak in Japan; Tchoupitoulas from a wild Norway rat in New Orleans, La.; Hallnas-I and Puumala from Clethrionomys glareolus trapped in areas where NE occurs in Sweden and Finland, respectively; and Prospect Hill-I from Microtus pennsylvanicus in Frederick, Md.; Girard Point from a Norway rat trapped near Philadelphia, Pa.; and others.

In addition to Hantavirus, genera within the Bunyaviridae are Bunyavirus (prototype, Bunyamwera virus), Nairovirus (prototype, Crimean/Congo hemorrhagic fever virus), Phlebovirus (prototype, Sandfly fever virus), and Uukuvirus (prototype, Ukuniemi virus). The five genera are serologically, morphologically, and biochemically distinct. The Bunyaviridae are generally spherical, measure 80-120 nm in diameter, have surface projections 510 nm in length that are anchored in a lipid bilayered envelope, and have a genome of single-stranded RNA consisting of three segments (Martin et al., 1985).

Hantaan virus virions include round particles that measure 98 nm in diameter and oval particles that measure 110 x 173 nm in length. Negatively stained virions have an enveloped surface with a square grid-like pattern. The virus is stable at pH 7.0-9.0 but is inactivated at pH 5.0. It is relatively stable at 4-20°C but is inactivated rapidly at 37°C. It can be stored at -60°C. It can be grown in A-549 and Vero E6 cells.

The natural hosts of all hantaviruses appear to be small mammals, primarily rodents.
Multiple species may serve as hosts in a given geographical area, and the strain of virus and likelihood of causing disease in man vary from region to region. Thus far, there are about five dominant virus-rodent-human disease (if known) associations:

(i) Hantaan virus: the field mouse Apodemus agrarius -- KHF in Korea and the severe form of EHF in China;

(ii) Puumala virus: the bank vole Clethrionomys glareolus -- NE in Eastern Europe and Scandinavia;

(iii) Urban and laboratory rat viruses: Rattus norvegicus -- moderate disease in people, mostly in Asia but occasionally in Europe;

(iv) Girard Point and other viruses from North and South America: Rattus norvegicus -- no disease recognized in humans although serological evidence of infection has been found; and

(v) Prospect Hill virus: the meadow vole Microtus pennsylvanicus -- no disease recognized in people.

Hantaviruses are transmitted to humans from persistently infected rodents and other small mammals.
In laboratory settings, this has usually been from laboratory rats or their tumors to people.
The major mode of transmission is respiratory infection by aerosols of urine, feces, and saliva containing infectious virus. Animal contact is not necessary as many visitors to infected animal facilities have contracted the infection. Animal bites can transmit the infection but appear to be of relatively minor importance.

Reservoir hosts of Hantaan virus show no clinical signs, but the virus appears in their lungs about ten days after infection and subsequently appears in the urine and saliva. Peak virus shedding occurs about three weeks after infection, but virus can be detected in the lungs for six months and occasionally for up to two years. Aerosols are the main method of transmission. The epizootiology of other Hantavirus infections is poorly understood.

Although hantaviruses appear to be worldwide in distribution, it should be emphasized that human disease due to these agents has been reported only in Europe and Asia. Serologic surveys of rats and other small mammals have given evidence of Hantavirus infections in many areas of the world where disease due to hantaviruses is not known to occur, including North and South America.

The clinical severity of Hantavirus infections in people varies according to geographic distribution of virus strains and, possibly, to other factors. KHF caused by Hantaan virus ranges from severe to mild. The incubation period is usually 2-3 weeks. Signs include fever, headache, muscular pains, hemorrhages (cutaneous petechiae or ecchymoses, hemoptysis, hematuria, hematemesis, melena), and proteinuria. About 20% of patients develop shock, severe hemorrhages, and renal failure (the "hemorrhagic fever with renal syndrome"). Mortality can be 5-10%.

Cases of NE in human patients in Scandinavia tend to be relatively mild, have few hemorrhagic features, and show a mortality of less than 0.5%. There is acute onset of fever, headache, nausea, and vomiting followed in 3-6 days by proteinuria, oliguria, hematuria, and thrombocytopenia. Oliguria persists only a few days and is followed by polyuria. Most patients recover within three weeks.

Characteristic lesions in human patients that die of KHF are retroperitoneal edema; diffuse myocardial hemorrhage in the right atrium of the heart; severe congestion, hemorrhage, and necrosis in the renal medulla; and hemorrhage and necrosis in the anterior lobe of the pituitary gland.

In the period from the early 1940s to the early 1970s there were recognized across Eurasia a large assortment of clinical syndromes in humans, most commonly referred to as hemorrhagic fevers. These included hemorrhagic nephrosonephritis in Russia, recognized around 1944, epidemic hemorrhagic fever (EHF) in China, recognized about 1942-1944, nephropathia epidemica (NE) in Scandinavia, Korean hemorrhagic fever (KHF) in Korea, EHF in Eastern Europe, and EHF in Japan.

During the Korean War thousands of cases of KHF, a syndrome often characterized by acute high fever, shock, hemorrhage, and renal failure, occurred in United Nations' forces and attracted worldwide attention. H. W. Lee et al. (1978) isolated the causative agent of KHF from the field mouse, Apodemus agrarius, and named it Hantaan virus. Following the discovery of successful cell cultures for Hantaan virus, a large number of Hantaan-related viruses were isolated and assigned to the genus, Hantavirus.

Naturally infected laboratory rats have been the source of Hantavirus infections in research personnel in Japan, Belgium, the United Kingdom, and France. In Japan alone, at least 126 human cases and one death have occurred. As of 1987, hantaviruses still had not been eradicated from all animal facilities in Japan. Wild rodents brought into the laboratory have caused human infections of hantaviruses in Korea and Russia.

Virus: Coronaviruses. RNA (RCV, SDAV, PRC, IBV, MERS-COV
HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1,
SARS-COV (which causes severe acute respiratory syndrome)) INDEX
http://www.nfrs.org/sdav.html (2015-10-15)
orig -- Ann Storey MSc FIBMS published in Pro-Rat-a 171, May/June 2009.

LINK 2: http://dora.missouri.edu/rats/
LINK 3: http://www.zoologix.com/rodent/Datasheets/RatCoronavirusSDAV.htm
LINK 4: http://emedicine.medscape.com/../300455-overview (2015-01-13)
LINK 5: http://avianmedicine.net/content/uploads/2013/03/32.pdf (2013)

Coronaviruses are from the family Coronaviridae and are single-stranded enveloped RNA viruses, the surface of which is covered by crownlike projections, giving the virus its name. Coronavirus has a pleomorphic but mainly rounded morphology and is 90 to 200 nm in diameter. It is enveloped with club-shaped surface projections (peptomers) about 20 nm long. Coronavirus replicates in the cytoplasm of the host cells. Recognized taxons are the infectious bronchitis virus (IBV), turkey coronavirus and at least nine mammalian species.

Six human Coronaviruses (HCoVs) have now been identified:
HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-COV (which causes severe acute respiratory syndrome), and MERS-COV (Middle East respiratory syndrome). These HCoVs appear to be established human pathogens with worldwide distribution, causing upper and lower respiratory tract infections, especially in children. Typically, HCoV infection follows a seasonal pattern similar to that of influenza, although Hong Kong researchers found that HCoV-NL63 infections mainly occurred in early summer and autumn.

This virus is spread via droplet and fomite exposure.
Long known to cause upper respiratory infections, coronaviruses were not felt to significantly cause pneumonia until relatively recently. However, the severe acute respiratory syndrome (SARS) pandemic in 2003 brought the ability of this virus to cause life-threatening pneumonia to worldwide attention (see Zoonotic Viral Pneumonia, below).

Sialodacryoadenitis is an infectious disease of rats caused by rat coronavirus (RCV).
This infection of rats has been recognised for many years but the causative agent was not discovered until 1970, when the first virus of this group was isolated. This virus was designated Parker's Rat Coronavirus (PRC) after its discoverer. A second virus, Sialodacryoadenitis virus or SDAV was discovered just two years later. These two viruses are very similar and are now considered to be strains of the same virus, namely Rat Coronavirus or RCV. Since then, several more strains have been reported, including CARS (not the same as CAR bacillus), RCV-BCMM, RCV-W and RCV-NJ.

This is a virus that mutates frequently and whose virulence can vary widely, from rat to rat, strain to strain and outbreak to outbreak.

Coronaviruses are widespread among mammals and birds, (one strain is responsible for SARS in humans) but are largely species specific. .. A related virus MHV, or mouse hepatitis virus is common in mice.

IBV is distributed worldwide and is not antigenically uniform.
Chickens are the main host and may develop respiratory signs, interstitial nephritis, visceral gout or egg shell problems with decreased albumen quality. In central Europe, antibodies against IBV have been demonstrated in owls and some Passeriformes.

Sialodacryoadenitis and rat coronavirus are inter-related viral infections that affect the nasal cavities, lungs, salivary glands and the Harderian gland that is close to the eyes in rats. These are highly infectious diseases that can be spread from rat to rat simply by being in the same vicinity as an infected rat. Aerial spread of the virus is common through sneezing by the infected rats. In addition, rats do not always show signs of being infected, making this virus an unexpected danger.

The severity of symptoms varies with the strain.
Generally if the strain is new to the population then it is likely to produce more severe symptoms, as the population has no resistance to it, this is the same for most infections though.

This is a common virus and most outbreaks pass off without deaths or serious illness.
However, when a more virulent strain does appear, it is important that committees act quickly to prevent the spread of the infection. This means stopping shows and 'gatherings' until the outbreak has subsided. However, this will not work unless individual members behave in a responsible manner and keep away from more 'informal' meetings.

RCV spreads rapidly among rats housed in open cages and presumably, at gatherings of rat owners and their animals. The infection rate is normally 100% of rats held in one place. Transmission appears to be primarily by droplets (sneezed out by infected rats) or by direct contact. However, RCV can survive for up to two days dried onto surfaces. Therefore, so called 'fomite' transmission (that is via cages, surfaces, clothes etc) may play a part. Intrauterine infection does not occur. Due to the rapidity of spread, most rats in a room will have had the infection and become immune within 3-5 weeks of the initial contact with the virus, even if some rats still have some symptoms left to resolve.

Likewise, care must be taken when bringing in rats from unknown or dubious outside sources.
These rats can often be the source of new disease strains even if they appear well. Therefore you should quarantine these rats for 2-3 weeks. Alternatively, if you do mix these rats in with your own, you will need to watch yours carefully for a few weeks. During this time, you should keep away from other rats.

Symptoms can vary from the subclinical (no detectable illness) to death.
... Early signs, especially in very young rats, include squinting, photophobia, lacrymation (runny eyes), production of porphyrin around the eyes and nose which may also appear on the inside of the forelegs as they attempt to wash themselves. Older rats usually develop sneezing and sometimes swelling of the salivary glands at the angle of the jaw (parotid) and up the sides (submaxillary). Swelling of the Harderian and lacrymal glands around the eyes may also occur. These early symptoms develop 4-6 days post contact. However, as the first rats infected often show only mild symptoms, it may be 2 weeks or more before you realise your rats are infected.

The eyes may then become severely inflamed, leading to keratoconjunctivitis.
This is not caused by clinical infection of the eye, but by the disrupted production of tears from the infected lacrymal and Harderian glands. If this does not get better quickly then the cornea may become opaque and ulcerated. The eye itself may become greatly enlarged (megaloglobus). Dark red encrustations may be present around the eyes and nose due to the porphyrin released from the damaged Harderian glands. Other affects include weight loss, because the rat often stops eating or drinking, reduced fertility and infection of the lower respiratory tract (trachea and lungs).

Anorexia and high mortality in young birds were common in affected flocks.
Emaciation, pancreatitis, enteritis, dehydration and nephritis are common findings at necropsy.

Like many respiratory viruses, RCV causes flattening and loss of the ciliated cells lining the passageways of the lungs etc. This leads to mucus buildup and subsequent activation of any bacterial respiratory pathogens who may be living there, including Mycoplasma and CAR bacillus. Pneumonia, accompanied by fluid build up in the lungs, is not uncommon in severe cases and is the most likely cause of death when it occurs.

On the whole, this virus is usually non fatal, although occasional outbreaks, ... can produce a significant number of deaths. Rats on steroids do not shed the virus for significantly longer than other rats. There is evidence that some strains of rats are more susceptible to serious illness than others.

Rats mostly cease producing the virus when they start producing antibodies, that is 10-14 days post infection. .. the symptoms may take longer than that to resolve. Usually it takes 4-6 weeks post infection for all of the symptoms to completely subside and some scarring in the respiratory tract may be left, leading to occasional snuffles. The odd rat may go on to develop full blown Mycoplasmal respiratory disease. Eye problems, including clouding and ulceration of the cornea and megaloglobus, can also resolve in 4-6 weeks. However, some rats damage their eyes while they are swollen and this can lead to loss of the eye due to secondary bacterial infection. A few may also be left with glaucoma.

Following infection, the rat appears to produce antibodies for around six months.
After this, while the rat does not produce symptoms if infected again with RCV, it can still shed that virus for another 7 days.

Coronavirus is rather unstable at room temperature and samples for isolation should be stored below -20°C. Shipment of infected material is recommended on dry ice or in 50% glycerol. Lyophilization, preferably in 10% glucose (also for deep freezing), provides adequate stability; however, lyophilized IBV has to be stored in a refrigerator for long-term survival. Coronavirus is sensitive to ether and chloroform, and it is assumed to be sensitive to commonly used disinfectants.

The virus can be killed (neutralized) by normal household disinfectants and temperatures of 83C.
Cool washes are probably not sufficient to kill this virus.

There is no treatment for this infection but supportive therapy can help.
This includes blanket administration of pain killers, such as soluble aspirin or Ibuprofen in the drinking water to nursing for the worst affected. Rats who are not eating or drinking, should be dropper fed in order to improve their chances. I have found that diluted Nutrical, sweetened milk with a spot of alcohol and Polyaid can all make a big difference to a rat's chances.

Antibiotics will not touch the virus but the use of chloramphenicol eye drops does help prevent secondary eye infections. ... rats with the worst respiratory symptoms may be helped by a course of an antimycoplasmal antibiotic such as Baytril or Doxycycline.

Histopathologic examination of submandibular salivary glands reveals degenerative changes including acinar and ductal epithelial necrosis, interstitial edema, squamous metaplasia of ductular epithelium followed by proliferation of hyperchromatic acinar cells. Chronic lesions include replacement of acini with fibrous connective tissue and an infiltration of lymphocytes. Similar lesions are present in the lacrimal and Harderian glands. The sublingual salivary gland (mucous gland) is usually not affected.

The most common diagnostic test is serologic screen using MFI and IFA.
Coronavirus PCR assays will help detect RCV or SDAV in acute infections.
SDAV PCR samples include Harderian gland or submandibular salivary gland. Lung is the optimal sample for PCR testing of RCV.

Not all rats infected with SDAV show symptoms; some become carriers and pass the virus to other animals in a colony. Serological detection of the virus is of limited value because it takes 2 to 3 weeks after initial exposure (i.e. 1 to 2 weeks after clinical symptoms appear) for a detectable immune response to develop. Therefore, testing clinically affected rats using only serology methods often yields false negative results. Molecular detection of this virus by PCR, in contrast, is rapid, sensitive and specific, and is useful even immediately following infection.

INDEX