In European hares a similar virus called European Brown Hare Disease affects Lepus in several countries, which causes a bit less inflammation but is still acute and highly fatal. This disease predated outbreaks of RVHD in the 1980s, and the original source may have been wild Leporidae (Lepus and Oryctolagus) imported from Europe to China{3773}.

Recently another rabbit calicivirus has been described which replicates in the small intestine but causes no disease.{3768}

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Hepatitis E

Hepatitis E may be a zoonotic disease shared with humans by rats and swine; in an outbreak in Nepal 5/23 rats in a village had evidence of infection. It is transferred by the fecal-oral route, usually by contaminated water. Many swine (in Nepal and in the US) have cross-reacting antibodies. In the US study, there may have been a link between human jaundice cases and hepatitis E infection in nearby swine. Swine also become jaundiced, a unique clinical sign in animal models of hepatitis.{3958} In humans the disease is acute and self-limiting, with the potential for high mortality. There have not been recorded cases of transmission in the lab animal environment.{4780}

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Family Flaviviridae

Flavivirus

Louping ill is a tick-borne disease of sheep in Great Britain and Ireland. Mortality (from CNS symptoms) is only about 10% on endemic farms, but may rise to 60% when ticks are feeding and the disease has not been present.{3997}

Wesselsbron disease is a mosquito-borne disease in African sheep and cattle, and resembles Rift valley fever. It is zoonotic. It causes abortion in cattle and sheep, and high mortality in neonatal lambs.{3997}

West Nile virus

West Nile (WN) virus has emerged in recent years in temperate regions of Europe and North America, presenting a threat to public, equine, and animal health. The most serious manifestation of WN virus infection is fatal encephalitis (inflammation of the brain) in humans and horses, as well as mortality in certain domestic and wild birds.

History: West Nile virus was first isolated from a febrile adult woman in the West Nile District of Uganda in 1937. The ecology was characterized in Egypt in the 1950s. The virus became recognized as a cause of severe human meningoencephalitis (inflammation of the spinal cord and brain) in elderly patients during an outbreak in Israel in 1957. Equine disease was first noted in Egypt and France in the early 1960s. The first appearance of WN virus in North America in 1999, with encephalitis reported in humans and horses, and the subsequent spread in the United States may be an important milestone in the evolving history of this virus.

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Hepatitis C

Only humans and chimpanzees are susceptible to hepatitis C virus, which is a common cause of hepatitis in humans.{3770}{3958} It was discovered when serum from a nurse who had suffered a needle-stick injury was given to two chimpanzees, which subsequently developed elevated liver enzymes and acute hepatitis, although they were clinically asymptomatic. Hepatocellular carcinoma is an uncommon outcome of hepatitis C infection in humans and is linked to cirrhosis. The virus is considered by some to be a "quasispecies" because it mutates frequently.{3958}

Pestivirus (hog cholera, BVD, Border disease)

Pestiviruses, including those causing bovine virus diarrhea, hog cholera and Border disease, can all cause developmental lesions in the CNS. In calves infected with BVD in utero the primary lesion is cerebellar hypoplasia or atrophy, but dysmyelination can also occur. Hog cholera can be teratogenic in porcine fetuses, also causing hypomyelinogenesis and cerebellar hypoplasia. In lambs and goats infected with Border disease virus in utero, there are skeletal lesions and hypomyelinogenesis.{4105}

Hog cholera affects swine of all ages, and is characterized by sudden onset, high morbidity and mortality, and diverse signs caused by different virus strains. It is endemic in South America, Africa, Asia and some European countries. It has been eradicated from the US, Canada, Australia and Britain. Early signs include diarrhea, hyperemia and fever. The skin becomes cyanotic. Nervous signs may include ataxia, paralysis or seizures. Congenital infection causes abortion, stillbirth or runting.  There is a live virus vaccine.{3997}

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Family Coronaviridae

Genus coronavirus

There are two MHV biotypes: respiratory or polytropic (most models) and enteric (more common and less pathogenic). The respiratory strains replicate in nasal epithelium causing minimal pathology, and then disseminate readily to target organs including the liver and lymphoid tissues where they induce focal necrosis with syncytia. CNS infection may result, with flaccid paralysis{3551}. The respiratory mucosa is not involved, only the vascular endothelium. Other causes of syncytium formation in the mouse include  Sendai virus, EDIM, and Mycoplasma. Athymic or scid mice infected with respiratory MHV have progressive multifocal necrotizing lesions in the nasal epithelium, liver, brain, bone marrow, lymphoid tissues and other organs.{4032}. Enteric strains remain in the gut (especially ascending colon and cecum, sometimes liver and brain) where they induce hallmark syncytia, and do not disseminate. Infant mice develop enteritis and die within 24 hours. Their villi are very elongated and the crypts are unresponsive, unable to replace the epithelium.{3763} Older mice repair their damaged mucosa better, resulting in self-limiting malabsorption and diarrhea. Immunocompromised mice infected with enterotropic MHV do not exhibit clinical disease.{4032}

Mouse susceptibility is partially dependent on genetic makeup, where it is passed as an autosomal dominant trait. C3H/RV mice are resistant to MHV-1 but semi-susceptible to MHV-3. DBA/2 mice are susceptible to MHV-3 and die acutely as adults, but A/J mice are resistant after weaning.{3551} Clinical signs are not pathognomonic; differential must include EDIM, mousepox, reovirus 3, Sendai virus, Tyzzer’s, salmonellosis, and CNS diseases such as mouse encephalomyelitis, M. neurolyticum toxicosis, neoplasia or musculoskeletal degeneration. If histology reveals syncytia in vascular endothelial cells, it is often MHV. If there is vascular endothelial hypertrophy, K virus or ectromelia should be considered. If the lesions look like syncytia but are not, one should think of Sarcocystis.{4032}

RT-PCR on feces can be used to pick up MHV, even when serology is negative{3823}. Gross necropsy and histology provide important clues-- focal necrosis, PMN and macrophage infiltration, syncytia (which may be seen also in vascular endothelium of other organs), hepatic and splenic enlargement, spotty liver, pitting, and fibrinous adhesions.{4033}

Control usually involves depopulation and strict monitoring of biological materials.{3551} Depopulation is necessary because of viral persistence in immunocompromised mice. It has been shown that sublethal doses of MHV can interfere with response to Trypanosoma cruzi; CBA mice infected with both pathogens died whereas those infected with only one lived.{3931} BALB/c sentinels are more susceptible than are C57BL/6.

Rat coronavirus (RCV) is common in laboratory rats. Like MHV, there are many strains of rat coronavirus, including Parker’s Rat Coronavirus and sialodacryoadenitis virus.{3763} Parker's rat coronavirus was the first coronavirus isolated from rats; it caused rhinitis, tracheitis and interstitial pneumonitis with high infant mortality. There are salivary and lacrimal gland lesions but these were originally overlooked.{4208} In SDAV infection, sialodacryoadenitis and interstitial pneumonia occur secondary to involvement of the upper respiratory tract. Necrotizing tracheitis, rhinitis and bronchitis occur first, followed by involvement of lower respiratory tissues, lacrimal glands and salivary glands. Harderian glands should be obtained for histopathology. The sublingual salivary glands are usually spared. Signs include cervical swelling, nasal and ocular discharge, photophobia, keratitis, megaloglobus, anestrus and fetal resorption. Athymic rats develop a chronic wasting disease because of the progressive pneumonia and salivary gland lesions.  RT-PCR can be used to detect SDAV from nasal and oral swabs. Cage swabs can also be used to detect the virus, and may be the easiest and most sensitive means of antemortem diagnosis. Alginate swabs work best. {4130}{4034} Vaccine may be prepared from either Parker's {3979} or other strains{3978} which provides partial protection for at least 6 months.

Rabbit coronavirus (which cross-reacts with other mammalian coronaviruses such as human 229E, FIP, canine coronavirus, and TGEV) probably arose as a contaminant of Treponema pallidum cultures, and occurs only in experimentally-infected rabbits. It is associated with three different disease states: (1) pleural effusion disease, (2) cardiomyopathy (the virus is antigenically related to human coronavirus 229E and the rabbit is a model), and (3) enteritis. In pleural effusion, fever is followed by pulmonary edema, right heart dilatation, peritoneal effusion, mesenteric lymphadenopathy, and necrosis of liver, kidney and lung. Iridocyclitis may also be seen. Histologically, one sees lymphoid depletion, focal degeneration in thymus and lymph nodes, proliferation in glomeruli, and uveitis. With the cardiomyopathy form, there is myocardial and diaphragmatic degeneration and necrosis, pulmonary edema, lymphoid depletion or hyperplasia. Death is due to congestive heart failure. The differential should include hypovitaminosis E, salmonellosis, pasteurellosis, encephalitozoonosis and anesthesia with detomidine. Only one natural outbreak of the enteric form of coronavirus has occurred. The virus has not been propagated in vitro, making further characterization difficult. The outbreak occurred in recently weaned, 3-10 week old rabbits in a barrier colony. Morbidity was 40-60% and nearly 100% fatal. With experimentally-induced infections mortality is much lower. The cecum is distended with watery, off white to tan feces. There is villous atrophy, vacuolation and necrosis of enterocytes, mucosal edema and mixed inflammatory infiltrate.{3773}{3768}{4731}

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Epizootic catarrhal enteritis is a newly-described coronaviral disease of ferrets. Morbidity is high but mortality is low. Older ferrets (approximately 4 years old)with existing disease are most severely affected, and have severe diarrhea; the stool is dark green in color and contains balls of unabsorbed fat and mucous. During recovery the stools take on a birdseed appearance. Microscopically, apical enterocytes undergo vacuolar degeneration and necrosis. The villi atrophy, fuse and become blunted. Later on there is lymphocytic enteritis. Treatment includes aggressive rehydration (up to 90ml/lb/day), amoxicillin at 10-20mg/lb, and a bland baby food diet. Ferrets that recover may shed virus for up to 6-8 months.{3767}{4098}

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Feline infectious peritonitis and feline enteric coronavirus: These two viruses are probably related, with FECV being the non-pathogenic one. FIP can infect macrophages, making it a systemic intracellular pathogen. Systemic antibodies are not protective; in fact, the immune response can possibly worsen the clinical disease because the macrophages that attack the antibody-antigen complexes then become hosts for viral replication. Disease is worse in young (<18 months) and old (>13 years) cats. It occurs as an acute vasculitis with pleural or peritoneal effusions, or as chronic granulomatous disease. There is no effective treatment, although a vaccine is available. The virus is stable at room temperature for weeks to months, but can be killed with disinfectants.{4649}

Genus Arterivirus

According to Dr. Barthold{3763}, the arteriviruses and the togaviruses are now grouped with the coronaviruses, whereas Fenner{3764} put arteriviruses as unclassified and gave togaviruses their own family. Equine arteritis is caused by an arterivirus.

Lactate dehydrogenase virus of mice (LDHV) is common in wild mice, causing persistent, permanent LDH elevation and subclinical disease. Demyelination has been produced in immunosuppressed AKR and C58 strains, but disease was associated with a retrovirus. The virus may contaminate transplantable tumor lines. It can be removed by passaging through nonpermissive species such as rats{3763}{3551}. The method for detecting infected cell lines used to be measurement of LDH levels in SPF mice before and 4 days after inoculation{3551}. A PCR assay is now available to screen tumor lines that are destined for mouse inoculation.{4185} However, caution must be used, as in at least one case the RT-PCR was falsely negative due to selection of a poor primer and/or interfering substances in serum.{4193} LDHV may be the most common contaminant of transplanted tumors.{4035}

Simian hemorrhagic fever is a reportable disease, as is any epizootic hemmorhagic fever in macaques. The virus is endemic in patas monkeys (Erythrocebus patas) and African species (African greens, baboons), which may remain viremic and asymptomatic for life. Transmission to macaques requires parenteral exposure to blood or body fluids, but once in macaques it is nearly 100% fatal in explosive epizootics. The virus spreads very readily among macaques by aerosol. Signs include fever, anorexia, depression, facial edema, epistaxis, skin and subQ hemorrhage, increased LDH, DIC and thrombocytopenia. Lesions are seen only in the final disease stages. Petechial hemorrhages are seen on the mucosal and serosal surfaces. The proximal duodenum becomes hemorrhagic and necrotic, the spleen enlarges, and splenic lymphoid follicles are ringed with a zone of bright red hemorrhage. Meningoencephalitis may occur.{3770} The disease must be differentiated from Ebola virus, which has more-or-less specific histologic lesions in the liver, adrenal and lung.{4082}

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Family Toroviridae

Genus Torovirus

Doughnut-shaped virus associated with diarrhea in horses as Berne virus and calves as Breda virus.

Family Orthomyxoviridae (influenza)

Ferrets are the only domestic animals which are susceptible to human influenza viruses. Aside from making them good models, pet ferrets may infect their human owners. Clinical signs include photophobia, catarrhal nasal discharge, sneezing, coughing, fever, anorexia and malaise. Lesions are rarely seen because the disease is relatively mild.{3767} If ferrets are fed an arginine-free diet, they develop Reye's syndrome after influenza infection. Signs include hyperammonemia, encephalopathy, prostration, coma, liver changes, and increased SGOT and SGPT.{4038}

A strain of influenza A virus (A/PR/8) was adapted to mice by serial passage. As a refinement, rectal temperature was measured daily for 14 days. The LD50 and the "HID50" (hypothermia-inducing dose) were the same; mice with body temperatures below 32°C had high morbidity and mortality.{4194}

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Family Arenaviridae, genus Arenavirus

Lymphocytic choriomeningitis (LCM) of mice: This is a zoonotic disease occurring most often in wild and pet-store mice, but it represents a hazard to laboratory mice by inadvertent inoculation with contaminated material. Mice, hamsters and humans are natural hosts, able to transmit virus. Most mice have subclinical infections because the virus is not lytic; but they shed virus, especially in urine, for long periods. The virus infects B cells, and surface antigens induce cellular immunity. Lesions develop because of this T cell-mediated response. Differential diagnosis includes MHV, mousepox, reovirus 3, and Tyzzer’s. In contrast, mice exposed in utero or as neonates develop tolerance with high virus titers. Tolerance eventually breaks down later in life to produce immune-complex glomerulonephritis ("late onset disease"). These mice can perpetuate infection in the breeding colony because they shed virus throughout their breeding lifespan, only developing late-onset disease at 9-12 months of age{3551}. If T cells from immune mice are transferred to subclinically infected ones, they develop the LCM disease state and die from T cell-mediated damage. In young adults the virus may cause lytic lesions of the white pulp of the spleen. In the liver, "piecemeal necrosis" is seen; this is similar to a hepatitis seen in tamarins which have eaten LCM-infected mice. Seropositive mice can be culled, and since mouse-to-mouse spread is slow, this may work to eliminate the disease in non-breeding mice{3763}{3551}

Guinea pigs have been infected mostly by experimental means with LCMV. They show posterior paresis, hepatomegaly and splenomegaly. Histologically they have lymphocytic infiltrates in the brain, liver, kidney, adrenal, and lungs. Diagnosis is by in situ tissue techniques, ELISA, IFA or MAP. Guinea pigs may also act as a source of infection for humans.{3775}

In NHPs, LCMV causes callitrichid hepatitis. Tamarins and marmosets in zoos are infected by being fed "pinkies" or coming in contact with wild mice. Some NHPs are found dead; others die after several days of weakness and anorexia, some with seizures and respiratory distress. Pathologic lesions include jaundice, subcutaneous/intramuscular hemorrhage, hepatosplenomegaly and pericardial effusion. Histologically the hepatocytes swell and die, WBCs infiltrate and portal phlebitis occurs. No inclusion bodies are present. Diagnosis is by EM in degenerate hepatocytes.{3770}

Humans are infected usually by aerosols, or by accidental inoculation. Humans develop a flu-like illness, but there can be more serious signs: rash, lymphadenopathy, meningoencephalitis; rarely, orchitis, arthritis and epicarditis with death in several cases. Pregnant women can transmit LCMV to their fetuses resulting in ocular abnormalities and either macrocephaly or microcephaly.{4780}

Lassa fever is carried by multimammate rats as the only known reservoir of human infection. There are no clinical signs in the rodents, but they shed virus in their urine. The disease first appeared in 1969 when a nurse in Nigeria contracted severe fever and died. Several others were also infected, including research workers in the US working with material from infected patients. In humans the signs are nonspecific, with variable signs of hemorrhagic fever. In endemic areas (west Africa), the disease may be asymptomatic or minor, with seropositive rates of 15-40%. It can be rapidly diagnosed by PCR since there is early viremia. The virus is easily cultured in Vero cells. Lassa fever is a reportable disease in most countries. Risk to casual contacts is negligible, since humans are infected mainly by eating either the infected rats or other food contaminated with rat urine. Person-to-person spread is mainly by contamination of broken skin by infected blood. It can be spread by sexual contact since virus is present in urine, saliva and semen. Some aerosol transmission is possible, which is unusual for arenaviruses. For more information, see www.science.mcmaster.ca/Biology/Virology/18/epidem.htm or www.coppettswood.demon.co.uk/lassa.htm.

Other arenaviruses include Guanarito, Junin, Machupo and Sabia, all found in South America.

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Family Bunyaviridae, genus Bunyavirus

Hanta virus (Korean hemorrhagic fever, murine virus nephropathy, Hantaan virus, hemorrhagic fever with renal syndrome=HFRS, Hanta pulmonary syndrome=HPR [NB the last two are considered by Barthold to be separate virus lineages]) is widespread in wild rats, but rare in laboratory rats. It is transmitted by aerosol and contact (other bunyaviruses spread by insects).{4208} Any disease occurring in wild rodents has not been thoroughly evaluated. In the US, Peromyscus spp. is the major reservoir. Inoculation of virus into Peromyscus or other permissive species must be performed in ABSL4 conditions{3950}. In humans, which are incidental hosts, the US origin virus causes acute pulmonary edema. In Asia the disease includes proteinuria, azotemia, petechiae, hemoconcentration, hypotension and renal failure.{3763} The Lewis rat may be a model for persistent Hantavirus infection, and inbreds have the advantage of being useful for studies of immunologic modulation. Rats develop persistent asymptomatic infection throughout the body, including the skin. This suggests that a route of spread may be through bites. The virus (Seoul strain) is endotheliotropic. Infected rats commonly develop insulitis and hyperglycemia due to pancreatic infection.{3976} Peromyscus have virus in the lung, liver, kidney, and spleen.{4208}

Akabane virus is an arthropod-borne virus causing abortion, stillbirth and congenital anomalies (arthrogryposis-hydranencephaly syndrome) in cattle, goats and sheep. Disease has been diagnosed in Japan, Taiwan, Australia and Israel. Recently it was diagnosed in five adult cows with normal appetite and temperature, and neurologic signs including hypersensitivity, tremor, ataxia and lameness.{4296}

Other bunyaviruses include phlebovirus (sandfly fever), nairovirus (Nairobi sheep disease), and uukuvirus (uukuniemi).

Family Reoviridae

Orthoreovirus (reoviruses of animals)

Mouse reovirus 1, 2, 3:  Virions are isometric, nonenveloped, and resistant to treatment with ether and acid. Mammalian reoviruses agglutinate human type O RBCs. Reoviruses 1 and 2 are uniform, whereas reovirus 3 has several subtypes.{4092} Reovirus 3 is a dsRNA virus that is relatively resistant to heat. This is a moderately-frequent subclinical disease, although the historic literature describes CNS disturbances, hepatitis, diarrhea and steatorrhea. Disease severity depends upon age: suckling mice develop acute disease (wasting, jaundice and oily hair are typical), older mice have chronic disease that is pantropic, and adults are subclinically infected{3551}. It is detected serologically.{3763} The differential diagnosis includes MHV, Tyzzer’s, and ectromelia{3551}.

Baboon orthoreovirus: In 1993 a small outbreak of acute, progressive encephalitis occurred in eight juvenile baboons (averaging 18 months of age) at the Southwest Foundation for Biomedical Research. The initial sign was hind limb weakness, which manifested itself as a range of signs from lameness to truncal ataxia. Seven of these progressed to paraplegia, and two became tetraparetic within 48 hours. Three animals showed progressive disorientation. Three had generalized Jacksonian seizures. Two had head tilt; one had vertical nystagmus. Progression was rapid and severe, with 7 animals being euthanatized and one dying 2-8 days after initial signs were noted. The possible incubation period ranged from 1-393 days. All but one animal were housed in the same gang cage. Two additional baboons and 25 Swiss Webster mice were inoculated intracranially with virus from one infected animal. The baboons were euthanatized 6 weeks later. Brain lesions in all baboons included lymphocytic perivascular cuffing in white and gray matter in the brain, spinal cord and meninges. The virus grows in Vero cells, in which it produces CPE including large syncytia with amorphous eosinophilic inclusions. Acridine orange causes the virus to fluoresce pale green; this is a classic test for double-stranded nucleic acids. Serology (ELISA and Western blot) indicated that stored baboon sera from as early as the 1970s reacted positively. Antibodies do not appear to neutralize the virus, a sign that animals may be persistently infected. This disease is of concern because baboons are considered for use in xenograft transplant experiments.{4092}

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Rotavirus

Epizootic diarrhea of infant mice (EDIM) is a typical rotaviral disease, commonly causing diarrhea, fecal soiling and runting in susceptible mice. The virus replicates in epithelial cells of the small intestine. All ages are susceptible but lesions are more common in those <12 days of age. Since disease is related to the turnover status of the GI mucosa rather than immune status, even SCID mice may not develop overt disease. The main histologic lesion is hydropic swelling of villous tips. Thymic atrophy may occur{3551}. Commercial ELISA detects the cross-reacting rotavirus, but false positives may occur with some feeds.{3763} It can be hard to diagnose because of the lack of good serological tests. Differentials include MHV, reovirus 3, Tyzzer’s and Salmonella. Control is achieved with microisolators and good sanitation; the infection can be allowed to burn itself out by cessation of breeding for 4-6 weeks{3551}.

Infectious diarrhea of rats (IDIR) is caused by either a reovirus or rotavirus, with pathogenesis similar to EDIM. Suckling rats <12 days old develop diarrhea, erythema of the anus and runting. The villi are attenuated, necrotic, and have syncytia of enterocytes with intracytoplasmic inclusions in the distal small intestine.{3763} The Army, quoting Percy and Barthold's book, says that the agent is suspected to be of human origin.

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Rotavirus group A serotype 3 is endemic in commercial rabbitries. Morbidity is high but mortality is low, except in weanling and suckling kits. Disease is usually acute and self-limiting. Clinical signs include dehydration and a distended, congested cecum, with watery diarrhea for 2-3 days. Histologically the findings are similar to coronavirus, with villous atrophy, blunting, fusion and vacuolation in the jejunum and ileum. Apical enterocytes are flattened and the lamina propria and submucosa are edematous. In the cecum there is desquamation with basophilic cytoplasmic debris. The differential diagnosis includes coronavirus, colibacillosis, coccidiosis and clostridial disease.{3768}{3773} Rotavirus is only mildly pathogenic, so coinfection with other pathogens should be considered if disease is severe. Maternal antibody is protective until about weaning time, when most rabbits are exposed and develop protective antibody titers. It is highly infectious, spreading from feces, on fomites and possibly by airborne spread. Control can be achieved by cessation of breeding for 4-6 weeks to allow the disease to run its course.{3773}

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Other reoviruses include coltivirus (Colorado tick fever), and aquareovirus of fish and shellfish.

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Family Birnaviridae, genus birnavirus

Infectious pancreatic necrosis is caused by a birnavirus in salmonid fish. Signs include fish spiraling around their long axis, abdominal distension, dark color, exophthalmia, and mucoid material in the intestine. Mortality is high. Pancreatic acinar tissue becomes necrotic.{3779}

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Family Retroviridae

Lentivirus

HIV-1, the cause of human AIDS, is a lentivirus. Its closest relative is probably SIV_cpz and the chimpanzee was the likely origin of HIV in humans. Among NHPs, pigtailed macaques (M. nemestrina) can be infected but do not become viremic or antigenemic, and gibbons don’t develop disease either although they become persistently infected. Gibbons are endangered and so are not a suitable model. Only the chimpanzee is easily infected with small amounts of HIV-1, seroconverts, and can produce infectious virus for a few weeks. Unlike humans, though, chimps develop an antibody response that induces complement-mediated lysis. They also don’t have CD4+ changes or opportunistic infections or any other disease signs.{3770, 4150}

HIV-2 causes "slim disease" in west Africa and appears to be much less pathogenic to humans than HIV-1. Its closest relative is SIV_smm in sooty mangabeys (Cercocebus torquatus) which are most likely the natural reservoir.{3770, 4150} Baboons and pigtail macaques are immunosuppressed, but other macaques are not affected.{3970}

Simian immunodeficiency viruses are a group of six related viruses occurring naturally in African primates, including Cercopithecus spp. (African greens), Papio spp. (especially the mandrill, P. sphinx{3970}), and Pan troglodytes. They are persistently infected but remain asymptomatic. Accidental hosts, such as macaques, develop fatal immunodeficiency for reasons that are unknown. The virus/host interaction appears to be critically important in determining the pathogenicity. In macaques, SIV_smm or SIV_mac are highly pathogenic, producing immunodeficiency disease that has many similarities to AIDS. Helper/inducer T cells (CD4+) are depleted. Initially there is a rash and lymphadenopathy. Eventually lymphoid tissues are depleted and opportunistic infections occur. Weight loss, diarrhea and anemia/thrombocytopenia occur. SIV is not oncogenic. SIV is considered to be a zoonotic agent, as a few workers have seroconverted.{3770, 4780} There are so many similarities between SIV and HIV-2 that the two are considered to be the same virus.{4039}

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Caprine arthritis/encephalitis virus (CAE) is widespread in goats, but does not naturally infect sheep. Infection occurs by transmission of fluids containing infected macrophages. Most frequently is spread through colostrum or milk from doe to kid. Horizontal transmission has also been documented; uninfected goats housed with infected ones will seroconvert. Venereal transmission and spread on fomites (dehorning equipment and needles) are also possible. Once the virus is integrated into host DNA, infection is life-long, despite immune response. The virus localizes in macrophages of the synovium (arthritis), lung (interstitial pneumonia), brain (leukoencephalomyelitis), and mammary gland (mastitis). A program of testing and culling is the best way to develop a CAE-free goat herd. Ovine progressive pneumonia (OPPV) and maedi-visna virus (MVV) are similar lentiviruses that infect sheep.{4518}

Spumavirus (foamy viruses)

Foamy viruses are nonpathogenic, but they are prevalent in macaque tissues and interfere with tissue culture work. They may mimic the cytopathic effects of other viruses, producing vacuolated multinuclear cells. Humans have become infected with macaque spumaviruses.{3770} The risk of transmission to NHP caretakers appears to be high, but even the longest-followed case developed no signs after 16-20 years and no transmission to the spouse or child.{4039}

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Subfamily Oncovirinae{3770}

Mammalian type B retroviruses

Murine mammary tumor virus (MuMTV) is like MuLV in that all mice carry endogenous virus in their genomes. Some exogenous viruses, like the Bittner milk agent, are maintained, i.e. in C3H mice, as a model.{3763}

Percy and Barthold include a lengthy discussion of the role of mouse retroviruses in mouse strain characteristics as well as disease.  Retroelements occupy over 37% of the mouse genome, and include replication-competent endogenous retroviruses such as MuLVs and MMTVs, which integrate as DNA into the genome, becoming proviruses. Long terminal repeats (LTRs) flank various genes such as gag, pro, pol, and env. LTRs confers tropism for particular tissues (i.e. mammary tissues) which is why MMTV LTRs are often used in transgenic constructs. Most proviruses are defective as well as often transcriptionally silent.

Exogenous MuLVs and MMTVs are not integrated into the host genome and are horizontally transmitted; these have been eliminated from laboratory mice and include such viruses as Friend, Moloney and Rauscher group of MuLVs, and the Bittner milk agent (MMTV-S).

Each inbred mouse strain has its own unique set of endogenous retrovirus and retroelement sites of integration, which originated from various retrovirus families. Mouse retroviruses are "mother nature's transgenes", using reverse transcriptase to integrate in dividing cells' genomes, causing insertional mutagenesis. The host immune response to its load of retroviruses may contribute to immune complex vasculitis and glomerolonephritis. NOD mice, for example, develop immune-mediated insulitis against endogenous retroviruses in the pancreatic islets.

The endogenous MuLVs are classified by their host species tropisms: ecotropic (mouse cells only), polytropic (mouse and other species), and xenotropic (other species but not the mouse). Examples of such mutations include the dilute (d) mutation in DBA mice (ecotropic virus inserted in the Myo5a locus); the hairless (hr) mouse mutation due to polytropic virus integration in the hr locus; and the rodless retina (re1) mutation due to integration of a xenotropic virus into the Pde6b locus. Other retroelements have contributed to many mutations, including athymia (Foxn1), stargazer (Cacng2), obese (Lep), and albino (Tyr).{4749}

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Mammalian type C retroviruses

Mouse murine leukemia virus (MuLV) is an endogenous retrovirus found in nearly all laboratory mice, but it is non-oncogenic. Over time and under different conditions and tissues it may undergo mutation and recombination to produce pathogenic virus. Disease may include neoplasia, demyelination, and "grayness".{3763} SWR/J mice are one of the few inbred strains that do not carry an endogenous ecotropic retrovirus, whereas AKR/J mice carry a provirus called Akv in their germline. Infection of SWR/J embryos with Akr virus resulted in a high number of embryonic deaths and a high rate (61%) of lymphoma over 14 months. This prototype MuLV may, therefore, be more pathogenic than was previously thought.{4115}

Cavian leukemia is caused by a type C retrovirus. The disease is widespread and spontaneous in inbred and outbred strains, affecting young adults. Clinical signs are lymphadenopathy in the cervical, axillary, and inguinal nodes, splenomegaly, and hepatomegaly. Infiltration and obliteration of many tissues by lymphoblasts takes place. Cavian leukemia has been used as a model of virus-associated neoplasia.{3775}

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Mammalian type D retroviruses

Type D retroviruses occur only in NHPs, not in humans (although a few seropositive individuals have been found). They are classified as follows:

SRV serogroups

[Note: the above can be detected in a nested PCR assay on peripheral blood monocytes{4040}]

Type D retrovirus from talapoins (Miopithecus sp.)

Exogenous viruses attack many macaques. Naturally-occurring infection in wild macaques has been identified in M. fascicularis/Indonesia, M. nemestrina/Indonesia, M. radiata/India, M. tonkeana/Sulawesi, and M. mulatta/China. The virus infects several cell types, including B cells, CD4+ and CD8+ T cells, macrophages, epithelial cells of salivary glands, intestine, mouth and Langerhans, and the choroid plexus. Virus is shed in saliva, and transmission involves biting, grooming and licking. It can also be spread on fomites, or via blood, milk, tears, urine, and vaginal secretions.{4128} Animal status varies: some remain seronegative, persistently infected shedders. The incubation period may be between 7-90 days.{4128} The occurrence of disease varies with the animal’s antibody status, as antibodies are neutralizing. Monkeys that die early in infection have no antibody and high levels of antigen. Those that survive but are persistently viremic have intermediate levels of antibody and antigen. Those that clear the infection have high antibody titers and no antigen. The disease may be enzootic or epizootic (in naive colonies). Clinical signs include those of immunodeficiency disorder with or without fibroproliferative lesions in retroperitoneal or subcutaneous sites. Retroperitoneal fibromatosis can be dramatic (also associated with rhesus rhadinovirus). Neutropenia, lymphopenia and anemia are common. Most eventually develop terminal diarrhea, weight loss, bacterial infections or other opportunistic infections.{3770} In a large facility with over 400 NHPs (rhesus, cynos and stumptails), more than 20 cases of unusual disease may have been related to SRV/D spread within the colonies. Diseases included acute fulminating anemia, myeloblastic leukemia, multiple myeloma, lymphoma, hepatic abscess, retroperitoneal fibromatosis and acute necrotizing ulcerative gingivitis (ANUG). Clinical signs also included lymphadenopathy, splenomegaly and diarrhea. Many of the monkeys also tested positive for simian parvovirus. {4128} In another report, two cynos that were SRV/D positive developed intracranial lymphomas, which were surprising. Lymphoma isn't unusual in SIV-infected NHPs (31-38% incidence in cynos), but had not been previously described in SRV-infected macaques. Presenting signs were of a lesion of cranial nerve III: ptosis and anisocoria.{4331}

SRV can be eradicated using a test-and-euthanatize program. Detection of positive animals can be challenging; both antibody (ELISA) and antigen (PCR or VI) testing is recommended.

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HTLV/BLV-like viruses

Baskin{3770} groups these with type C retroviruses. They have the tat gene and include BLV, HTLV-I and II, and STLV-I.

Simian T-cell leukemia virus-I (STLV-I) is an important model for human T cell leukemia/lymphoma. Other human diseases are tropical spastic paraparesis and an HTLV-associated myelopathy. Many Old World NHPs are naturally infected, such as baboons, African green monkeys, Patas monkeys, some macaques, and chimpanzees. Disease incidence is higher in females and those >16 years of age. Transmission is through sexual contact. STLV-I infects CD4+ T cells of macaques and CD8+ T cells of African greens. Most NHPs remain asymptomatic. However, leukemia/lymphoma has occurred in baboons, African greens and macaques. Tumorigenesis is related to tax, a non-structural gene that causes cell activation, i.e. via the IL-2 receptor. This relationship is poorly understood and is the reason for using STLV-I as a model for the human disease.{3770}

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Order Mononegavirales

Linear negative sense ssRNA, including Paramyxoviridae, Rhabdoviridae, and Filoviridae

Family Paramyxoviridae, Subfamily Paramyxovirinae

Genus Paramyxovirus

Pneumonia virus of mice (PVM) is common in laboratory mice and rats. The virus, like Sendai, is ssRNA and replicates in the cytoplasm. It is heat-labile.{3551} Immunocompetent mice have subclinical upper respiratory infection. Nude and SCID mice, however, may develop a chronic wasting disease due to pneumonia affecting bronchiolar epithelium and type 2 pneumocytes.{3763} 

In rats, the virus does not cause clinical disease, but there are lesions of multifocal, nonsuppurative vasculitis and interstitial pneumonitis{4757}{3763}. One way to rid rat colonies of PVM is to isolate pups at weaning from the rest of the infected colony. Although they may still receive maternal immunity, this is undetectable by 4 weeks of age, at least by ELISA at 1:5 and 1:50.{4036} It is present in hamster colonies without clinical disease{3775}. Diagnosis is based mostly on serology, since natural infection is inapparent. HAI, IFA, VI and ELISA are available.{3551}

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Sendai virus (parainfluenza I{3764}) is the most significant viral disease of mice, due to its ability to cause disease in all ages. Natural hosts include mice, rats, hamsters, and guinea pigs, although only mice show clinical signs. Experimentally-infected ferrets may have severe pneumonia. The virus is ssRNA and the envelope is lipid-solvent sensitive. It is highly contagious, and morbidity is 100% via aerosols and contact. Disease outbreaks in susceptible mice may appear as acute clinical disease, or as inapparent enzootics detected by serologic screening.{3551} Sendai virus infects respiratory epithelium and type 2 pneumocytes, but is not lytic. Disease results from the immune system’s attack of infected cells (so nude and SCID mice develop hyperplasia without necrosis). Signs include necrotizing rhinitis, tracheobronchitis, bronchiolitis and interstitial pneumonia. During recovery, hyperplasia and squamous metaplasia occur with focal fibrosis. Mice strains vary in susceptibility because of mucociliary clearance. Most susceptible strains include 129/ReJ, 129/J, Nude (Swiss), DBA/1J, DBA/2, and C3H/Bi. Resistant strains include AKR/J, Swiss, C57BL/6J, RF/J, and SJL/J.{3551} Secondary bacterial infection may cause respiratory signs and ear infections.{3763} Differential diagnosis includes other pneumonias, such as PVM (milder, asymptomatic), bacterial pneumonias (morphologically and culturally different), and murine respiratory mycoplasmosis. Control is achieved by letting the infection "burn itself out" over 6 weeks, as carriers and latency are not known to occur. There is a killed vaccine available for valuable mice. The virus can compromise immunologic studies, as it interferes with response to mitogens, inhibits growth of transplanted tumors, and its pulmonary lesions can confound interpretation of other lesions.{3551} FELASA recommends testing for Sendai virus every 3 months in mice, rats, hamsters and guinea pigs.

Clinical case presentation

Sig: Adult and suckling mice, DBA/2, in a facility with high humidity and low air turnover. Nudes and immunosuppressed mice develop signs later.

Clinical signs: hunched position, piloerection, rapid weight loss, dyspnea, chattering sounds, crusty eyes. Immunocompromised mice develop wasting disease. Mortality varies from 0-100% depending on strain.

Gross necropsy: partial to complete lung consolidation. Individual lobes are meaty and plum-colored, cut surface exudes frothy serosanguinous fluid. Pleural adhesions and fluid in the pleural space and pericardial sac in later cases.

Histopathology: Type II pneumocytes (not usually type I) affected. Mouse genotype alters the response, with susceptible strains having bronchopneumonia and interstitial pneumonia.  Susceptible hosts mount a more florid response, exacerbating the pathology. Immunocompromised hosts have prolonged acute phase responses leading to wasting and death. Inflammatory edema of bronchial lamina propria extends to alveoli and pervascular spaces. Necrosis and exfoliation of bronchial epithelium follows, with debris accumulating in airways and alveolar spaces. Interstitial pneumonia is caused by infiltration of alveolar septae with leukocytes.

Differential diagnosis: PVM (generally milder or asymptomatic), mycoplasmosis (sporadic, looks different histologically), secondary bacterial pneumonia.

Transmission: highly infectious, aerosol-transmitted, 100% morbidity. Can be enzootic in postweaning mice.

Control: eliminate exposure of susceptible animals, by burn out for 4-6 weeks. Sendai is highly labile so sanitation works.

Sendai virus is now rare in rats, which usually are subclinically or mildly infected. Infant mortality may occur.{3763} Rabbits are susceptible to experimental infection but they remain asymptomatic and virus stays in the upper respiratory tract.{3768} Hamsters are commonly infected with Sendai, but confirmed clinical disease is rare. Neonatal Syrian and Chinese hamsters may be natural hosts, and develop fatal disease. In other cases only mild necrotizing bronchiolitis and interstitial pneumonia occur.{3775}

Saguinus mystax has been experimentally (and possibly also naturally) infected with Sendai virus and parainfluenza virus strain 3 (HA-1). Signs in adults included sneezing, weight loss, nasal discharge and conjunctivitis.{2765} A 1983 outbreak in a marmoset colony (Callithrix jacchus) involved 2/3 of the 91 animals, of which 10 were killed due to disease. Signs were sneezing, oculonasal discharge, depression and anorexia. Necropsy showed extensive congestion and/or consolidation of the lungs with no other abnormalities. Histopathology revealed acute interstitial pneumonia. Electron microscopy revealed the presence of paramyxovirus which was initially thought to be measles; subsequent immunofluorescence showed the viruses to be parainfluenza type I, which is very similar or identical to Sendai virus.{4755} As these viruses are common causes of respiratory disease in children, they should be kept away from callitrichids in open colonies.

Parainfluenza virus (types I and II) can cause hydrocephalus in neonatal mice, hamsters and dogs. The virus causes stenosis of the aqueduct that results in a non-communicating form of hydrocephalus. In neonatally-infected animals there are no histologic signs of inflammation or presence of the antigen in the aqueduct; but in mice infected with influenza virus as adults there will be a glial response at the site of stenosis.{4105}

A brief mention was made in one paper that guinea pigs are commonly seropositive for a virus called "SV5", referred to as "a simian paramyxovirus" that was not considered problematic for this study.{4136}

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Hendra virus was first recognized in 1994 after an outbreak affecting racehorses and humans occurred in Queensland, Australia. Infection appear to have been acquired from intimate contact with infected horses via probable exposure to blood or other body fluids or excretions.

Hendra virus can infect more than one species of animal. Scientists believe fruit bats (also known as flying foxes) are the natural 'host' of the virus. This means the virus is carried by fruit bats, but has little effect on them. However, when it is transmitted to humans, horses, and other animals its effect can be lethal. Experimental studies have shown that in horses and cats the virus can cause fatal pneumonia.

Animals infected with Hendra excrete the virus in their urine.

CDC has developed a serological test for Hendra IgM. The virus has been classified as a genus with the Paramyxovirinae family and is being studied at Biosafety Level-4.

(Above is from http://www.cdc.gov/od/oc/media/fact/hendra.htm)

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Newcastle Disease: Newcastle disease causes severe economic losses in chickens. It is a reportable disease according to the International Animal Health Code. It spreads to humans by aerosol, causing follicular conjunctivitis that resolves spontaneously. Adult birds get anorexia and respiratory disease, while juveniles get neurologic disease.{4780} The virus is synonymous with avian paramyxovirus 1 (APMV-1) and belongs to the family Paramyxoviridae, subfamily Paramyxovirinae, genus Rubulavirus. It is a ssRNA virus, negative sense. Pigeon paramyxovirus (PPMV-1) is a variant of NDV that emerged in the Middle East in the 1970s and spread worldwide. There is a need to determine the risk of PPMV causing disease in chickens. The virus has been used to infect chickens experimentally. This study was done using "BSL-3 agricultural conditions". Although the chickens infected experimentally in this study did not show signs of disease, there was histologic evidence of lesions of the brain, heart and lymphoid organs. Pigeons should be considered as a potential source of NDV infection and should be vaccinated.{4307}

Genus Morbillivirus (measles)

Measles is a zoonotic disease of humans that can spread to apes, macaques, baboons, African greens, marmosets, tamarins, and squirrel monkeys. Most wild-caught OWM will be serologically positive within weeks of capture. The disease (in OWM) resembles distemper in puppies, with high morbidity and low mortality. Some infections are subclinical; others cause maculopapular rash (i.e. very tiny vesicles, c.f. varicella), conjunctivitis, facial erythema, respiratory difficulty (OWM), and diarrhea (NWM).

New World monkeys are more vulnerable and likely to die from measles. A devastating outbreak of measles killed 326 callitrichids (S. oedipus, S. fuscicollis, and C. jacchus) in an open colony in the 1970s. Clinical signs included swollen eyelids and lethargy, with death in less than a day. Lesions were interstitial pneumonitis with giant cells, multinucleated cells with intranuclear inclusions, and alveolar giant cells. Callitrichids are exquisitely sensitive to experimental infection.{2765} Both intranuclear and intracytoplasmic inclusion bodies are seen histologically. A female tamarin died with signs of diarrhea and hypothermia and was found to have measles based on immunohistochemistry. The take-home lesson was that, in tamarins, measles causes GI rather than respiratory signs, is extremely infectious, and results in high mortality.{4549}

Measles virus is immunosuppressive, and infection interferes with some research.{3770} Don't confuse measles with simian varicella, in which the animals develop vesicles and high liver enzymes. Vaccination of juvenile rhesus with two doses of canine distemper-measles vaccine at 3-month intervals provided higher titers than did the human measles vaccine.{4037}

SSPE in ferrets.htm

Subacute sclerosing panencephalitis (SSPE) is a rare CNS disease of children and adolescents caused by a defective measles virus. If strain D.R. is inoculated into the brains of young adult male ferrets, a very similar syndrome occurs. Tremors, seizures and hindlimb paralysis occur first; the signs last for days or weeks and end in death. The virus grows in the brain, and antibodies are synthesized there. The histologic lesion is perivascular cuffing with inflammatory infiltrates.

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Family Rhabdoviridae

Lyssavirus (rabies)

There has been only one spontaneous case of rabies reported in an NHP, published in 1966.{3770} Signs in humans include a prodromal phase of apprehension, headache, malaise and fever. This is followed by an acute neurologic phase with intermittent periods of excitation or nervousness, which progresses to paresis or paralysis, inability to swallow, delirium, convulsions and coma. Diagnosis of Negri bodies in Ammon's horn of the hippocampus and other brain and salivary gland sites is by direct flourescent antibody test. Other tissues may be tried, such as corneal impression smears, mucosal scrapings or skin biopsies. Rabies should be considered whenever a wild-caught or random-source lab animal shows encephalitic signs.{4780}

Infectious hematopoietic necrosis is caused by rhabdovirus that infects salmonid fish. Mortality is nearly 100%, with necrosis of hematopoietic tissue in the kidney and spleen. Affected fish have darker color, exophthalmia, abdominal distension, hemorrhage and anemia; a fecal cast may trail from the anus. The disease occurs at water temperatures of 10C, suggesting that it might be treated by raising the temperature. Another rhabdovirus causes viral hemorrhagic septicemia in European salmonids (especially rainbow trout) and Pacific Cod.{3779}

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Family Filoviridae, genus Filovirus (Marburg and Ebola)

Although filoviruses are not new, the first recorded outbreak did not occur until 1967, when 23 cases occurred in humans working with blood and tissues from newly-imported African green monkeys in Marburg, Germany. Protective clothing and modern precautions against virus transmission were not in use. Since then, a total of 23 outbreaks have occurred, with 1100 human cases of which 800 died. Most often, direct and intimate contact with patients is necessary, with nosocomial transmission important in sustaining outbreaks.{4082} 

The genus contains only two types, Marburg and Ebola, which are quite different from each other. Marburg was diagnosed in the early outbreaks among African green monkeys and affecting 34 people, but it has not been seen since a single case in 1987. Ebola has four subtypes. The most pathogenic for humans is Ebola/Zaire, the cause of two large outbreaks in Northern Democratic Republic of the Congo. The first occurred in 1976 and affected 318 people; the most recent occurred in 1995 in the town of Kikwit and affected 315 people. Ebola/Zaire was also the cause of the most recent outbreaks in 1996 in Gabon. Twenty human cases were exposed to a dead chimpanzee found in the forest, and 11 more cases occurred. Ebola/Sudan was the cause of 284 cases in 1976 that started with factory workers and spread to a hospital. Ebola/Ivory Coast was first documented in 1992 when there were 8 deaths in wild chimpanzees; another outbreak of 12 wild chimpanzees occurred in 1994-95, but there have been no human infections.{4082} Ebola-Reston virus has only been found in cynomolgus macaques imported from the Philippines and is less zoonotic than the others. Humans have been infected but no illness resulted. It was first diagnosed in cynomolgus macaques imported from the Philippines in 1989; four animal workers seroconverted. {3770, 4082} 

Filoviruses are BSL-4 pathogens. They are pleomorphic in appearance, with filamentous, branched, U-shaped, 6-shaped or circular configurations. Diagnosis is best achieved with ELISA and Western blot, although many other means have been used to detect IgM or IgG including complement fixation, indirect immunofluorescence and dot-immunobinding. Inoculation of cell culture or guinea pigs is frequently used to study the virus. Other species that have been experimentally infected include squirrel monkeys, Aedes egypti mosquitoes, hamsters and mice. The preferred human diagnostic specimen is serum or whole blood frozen on dry ice or nitrogen.{4082}

Symptoms in non-human primates include fever, weight loss, anorexia, cough, lethargy, coma, hemorrhage, rash and diarrhea with high LDH and thrombocytopenia. The incubation period is 2-14 days. Blood may fail to clot after death. There is no evidence of persistence. Gross lesions consist of a maculopapular rash, splenomegaly, petechiation, hemorrhage in the proximal duodenum and interstitial pneumonia. There is also necrosis of the liver, adrenal cortex and pulmonary bronchiolar/alveolar epithelium, which tend to distinguish Ebola from simian hemorrhagic fever, the major differential diagnosis. Amphophilic inclusions are found in many tissues including liver, adrenal, and spleen.{3770, 4082}

Treatment of infected humans involves use of strict barrier procedures to protect medical personnel and families, maintenance of adequate blood volume and electrolyte balance, treatment of cerebral edema, renal failure, coagulation disorders and secondary infection. Only one study has documented successful use of antiviral drugs against Ebola, in experimental mice. Controlled studies are needed, using guinea pigs, mice, and macaques, to develop better treatments. Killed virus vaccine seems to protect guinea pigs and mice, but safety concerns support development of a recombinant vaccine. Unfortunately, there does not seem to be good cross-protection against subtypes of filovirus in experimental animals.{4082}

The reservoir of Ebola and Marburg is still unknown, despite intensive searching. Bats have been the focus of most investigations. Vector transmission (via mosquitoes or soft ticks) has not been ruled out. Primates are probably not the reservoir, as the disease is highly fatal in them. In humans, transmission by direct contact with blood or tissues seems to be required, but in macaques aerosol transmission to a distance of 3 meters has been documented. The virus may persist in human seminal fluid for several months.{4082}

Recent recommendations from the CDC for quarantine of imported NHPs includes a 31-day period; but others have recommended a 60-90 day quarantine. Serology is of questionable value during quarantine or to detect infected animals. It is unknown whether eradicating seropositive animals would have any effect on eradicating the virus from a colony. Virus can only be isolated for 20 days after infection in a surviving monkey. Viral detection should only be used to diagnose disease in recently imported or otherwise suspect animals.{4082}

Personnel working with quarantined animals that might be carrying filoviruses need follow only routine procedures. Accidental exposure should be treated with vigorous soap and water cleansing or use of an eyewash. People potentially exposed to filovirus should be isolated, counseled, and placed in an appropriate risk category. High-risk exposures should have periodic blood sampling and daily body temperature monitoring.{4082}

Filoviruses are sensitive to ordinary disinfectants, autoclaving (60°C for 20 min), soaking in 2-5% bleach, UV light, gamma irradiation, formalin, ß-propiolactone/acetone, quaternary amines, phenolic disinfectants, and lipid solvents.{4082}

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Unclassified viruses

Hepatitis D virus

A human satellite virus dependent upon simultaneous hepadnavirus replication.

Astroviruses

Found in feces of calves, lambs and man.

Borna Disease virus

Encephalomyelitis of horses and sheep.

Subacute Spongiform Encephalopathies (Prions)

Highly resistant to inactivation, no nucleic acid found; produce slow infections followed by progressive disease and brain degeneration; prototype is scrapie; also mink encephalopathy, wasting disease of mule deer and elk, mad cow disease.

Chronic Wasting Disease

Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy (TSE) of North American deer and elk. First recognized as a clinical "wasting" syndrome in 1967 in mule deer in a wildlife research facility in northern Colorado, it was identified as a TSE in 1978. CWD is typified by chronic weight loss leading to death. There is no known relationship between CWD and any other spongiform encephalopathy of animals or people.

Species that have been affected with CWD include Rocky Mountain elk, mule deer, white-tailed deer, and black-tailed deer. Other ruminant species, including wild ruminants and domestic cattle, sheep, and goats, have been housed in wildlife facilities in direct or indirect contact with CWD-affected deer and elk. No cases of CWD or other TSE's have been detected in these other ruminant species.

Most cases of CWD occur in adult animals. The disease is progressive and always fatal. The most obvious and consistent clinical sign of CWD is weight loss over time. Behavioral changes also occur in the majority of cases, including decreased interactions with other animals in the pen, listlessness, lowering of the head, blank facial expression, and repetitive walking in set patterns within the pen. In elk, behavioral changes may also include hyperexcitability and nervousness. Affected animals continue to eat grain but may show decreased interest in hay. Excessive salivation and grinding of the teeth are seen. Most deer show increased drinking and urination.

Currently, definitive diagnosis is based on necropsy examination and testing. Gross lesions seen at necropsy reflect the clinical signs of CWD, primarily emaciation and aspiration pneumonia, which may be the cause of death. On microscopic examination, lesions of CWD in the central nervous system resemble those of other spongiform encephalopathies. In addition, immunohistochemistry of brain tissues reveals the presence of the abnormal prion protein.

Slow virus disease models.htm

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