VIRAL DISEASES
I. Myxoma Virus
II. Rabbit (Shope) Fibroma Virus
III. Rabbit (Shope) Papilloma Virus
IV. Rabbit Oral Papilloma Virus
V. Viral Hemorrhagic Disease (Viral Hemorrhagic Fever, Viral Necrotizing Hepatitis)


I. Myxoma Virus
A. Etiology: Myxomatosis is caused by any one of several strains of myxoma virus, a member of the leporipoxvirus group. Virulence of the different strains ranges from a mortality incidence of 99% in European rabbits to less than 30%. Incidence is high in endemic areas in the Pacific coastal states.
B. Transmission: The principal mode of transmission is via arthropod vectors (mosquitoes, fleas, flies, gnats). Transmission may also occur by contact with infected material from ocular discharges or oozing skin lesions of infected rabbits, contaminated spines of thistles, and the claws of predatory birds. Virus-infected skin nodules on wild rabbits, Syvilagus sp., are reservoirs of the agent.

C. Symptoms: In domestic rabbits, the clinical disease picture is largely predicated by the strain of virus involved as well as genetic resistance of the breed of rabbit.
California Strain of Virus: In the peracute form, rabbits die within a week of exposure showing slight edema of the eyelids and depression immediately prior to death. With the acute form in which rabbits survive for 1 to 2 weeks, symptoms are edema of the eyelids resulting in a droopy appearance of the eye; inflammation and edema around the anal, genital, oral, and nasal orifices; skin hemorrhages; and convulsions. A nodular lesion develops at the site of inoculation with both forms, but it is not a clearly defined tumor.

Standard Laboratory Strain of Virus: This strain induces a mean survival time of 11 days. Around 3 to 4 days post inoculation, a primary tumor becomes evident, and generalized tumors are seen on the 6th or 7th day. At this time, a mucopurulent nasal discharge and pronounced edema of the eyes and base of the ears are seen. By day 10, hard lumps cover much of the body.
European Strain of Virus: This strain is characterized by rapid proliferation of large lumps by day 7. The lumps may break open by day 10 and release a serous discharge. Lumps may occur on any area of the body. There is also pronounced edema of the face and anal regions, seropurulent discharge from eyes and nose, and considerable skin congestion.
D. Pathology: The most prominent gross lesions are skin tumors and pronounced cutaneous and subcutaneous edema. Skin hemorrhages and subserosal petechial and ecchymotic hemorrhages in the stomach and intestines may be observed. Various degrees of congestion will occur in the visceral organs depending on the severity of the disease. Skin tumors result from an initial proliferation of undifferentiated mesenchymal cells in the dermis which become large stellate cells termed myxoma cells. These cells lie in a homogeneous matrix of mucinous material. Necrosis can be observed in the center of this area. Epidermal cells overlying the tumor may appear normal in early stages of the tumor proliferation, or they may show hyperplasia or degeneration in later stages. Intracytoplasmic inclusions (arrows) are observed most commonly in cells of the prickle-cell layer of the epidermis, and in the stellate myxomatous cells.

F. Diagnosis: A diagnosis can be made from the clinical and pathological picture, virus isolation, and PCR amplification of viral sequences from tissue specimens. Serological tests including fluorescent antibody techniques, plaque-neutralization, and ELISA have been developed but are not commercially available.
G. Control: Control is achieved through vector control and adequate screening of the rabbitry, by quarantine of new animals, and isolation of all sick animals. A common practice, once a death from myxomatosis is diagnosed, is to cull all rabbits whose body temperature exceeds 104oF in an attempt to remove animals incubating the virus before shedding occurs. A vaccine was developed but has not been used as the vaccine caused clinical myxomatosis in some vaccinated rabbits.
II. Rabbit (Shope) Fibroma Virus
A. Etiology: Fibroma virus is a member of the leporipoxvirus group and is closely related to myxoma virus. The virus has widespread incidence in both domestic and wild rabbit populations. Few cases of virus-induced fibromas have been diagnosed in rabbits in Missouri although the majority of cases are reported from the western and southwestern United States.
B. Transmission: The natural transmission cycle is not known although arthropod vector transmission is likely.
C. Clinical Signs: Tumors occur on the legs or feet, on the muzzle, and around the eyes. The tumors are subcutaneous and not attached to underlying tissue. Metastases from the original tumor do not occur. The infected adult rabbit remains clinically normal otherwise. Tumors will typically regress after a period of months. Spontaneous and experimental infections of neonatal domestic rabbits, however, has produced cutaneous and visceral tumors.
D. Pathology: The earliest lesion is slight thickening of the subcutaneous tissue followed by development of clearly demarcated soft tissue swellings which are evident on day 6 post inoculation. Tumors increase in size until day 12. They persist for months before regressing. The earliest microscopic lesion is an acute inflammatory reaction followed by localized fibroblastic proliferation. Proliferation continues until a distinct tumor is formed consisting of spindle-shaped and polygonal connective tissue cells with abundant cytoplasm. Intracytoplasmic inclusions are present in stellate cells, and less commonly or rarely in the epidermal cells. Degeneration of the epidermis overlying the tumor may result from pressure ischemia. This leads to necrosis and sloughing of the epithelium.
F. Diagnosis: Clinical signs and lesion morphology are primary diagnostic tools.
G. Control: This is not considered to be an important problem in domestic rabbits. In outdoor rabbitries, vector control is advised.
III. Rabbit (Shope) Papilloma Virus
A. Etiology: A member of the papovavirus group. This disease is seen most frequently in cottontail rabbits of the Midwest with outbreaks in domestic rabbits. Incidence of disease is low.
B. Transmission: Arthropod vector transmission of the natural disease has been demonstrated. The mosquito is thought to be the main vector in transmission from feral to domestic rabbits.
C. Clinical Signs: Horny warts are found on the eyelids and ears. The growths are well keratinized, and the upper surface is irregular and split. The growths are easily scratched or knocked off. These sites later heal without complication.
D. Pathology: The tumor has the typical appearance of a papilloma with elongated rete pegs of epithelium surrounding central cores of connective tissue. A mild inflammatory cell infiltrate is normally found in the dermal layers underlying the tumor. Failure of the lesion to resolve may lead to development of squamous cell carcinoma.
E. Diagnosis: Clinical signs and histological examination are the basis for diagnosis.
F. Control: Control of the arthropod vectors will eliminate the introduction and spread of disease. Tumors that fail to spontaneously resolve in 30 days should be removed surgically to prevent dedifferentiation into neoplasia.
IV. Rabbit Oral Papilloma Virus
A. Etiology: A member of the papovavirus group, this virus is the only member of the papovavirus group having the domestic rabbit as its natural host. There is moderate incidence of disease.
B. Transmission: Spread is by direct contact of oral secretions containing sloughed epithelial cells from the oral warts. Infection occurs in the abraded epithelium of the tongue.
C. Clinical Signs: This is a benign disease characterized by numerous whitish growths on the underside of the tongue, oral cavity epithelium or gingiva. These later become pedunculated and ultimately ulcerate. The growths regress when the rabbit becomes immune.
D. Pathology: A typical papilloma with verrucous epidermal hyperplasia with rete peg formation and hyperkeratosis and dermal fibroplasia has been described. Intraepithelial viral inclusion bodies are not usually seen on microscopic examination of tumors.
E. Diagnosis: The gross lesions are diagnostic.
F. Control: No control measures to prevent exposure are known. Recovered rabbits are resistant to reinfection.
V. Viral Hemorrhagic Disease (Viral Hemorrhagic Fever, Viral Necrotizing Hepatitis)
The disease was first reported in China in 1984, and has since been reported in Europe, parts of Asia, Mexico and the United States.
A. Etiology: A calicivirus has been recovered from infected rabbits. Apparently strains of virus with varying degrees of virulence have been recovered from rabbits from different parts of the world.
B. Transmission: The agent can be spread by direct contact, biting arthropods and fomites, including handling of infected rabbit meat and by-products.
C. Clinical Signs: The incubation period ranges from 1 to 3 days, at which time one of three forms of the disease may be seen. The peracute disease is manifested by death without clinical signs. In acute disease, acute onset of anorexia and lethargy occur followed by labored respiration. Body temperature may be elevated from 40 to 41oC, but rapidly declines prior to death. In subacute disease, clinical disease progresses to include bloody nasal discharge, opisthotonus and vocalization. Death occurs 2 to 3 hours after the onset of clinical signs. In colony settings, morbidity may reach 90% with 100% mortality.
D. Pathology: Tracheal hemorrhages, petechia on the myocardium, kidney, and spleen, pulmonary edema and congestion, and widespread hepatic necrosis are frequently observed at necropsy.
E. Diagnosis: The disease is tentatively diagnosed based on the rapidly fatal infection and gross necropsy findings. VHD-specific PCR is used to confirm the postmortem diagnosis.
F. Treatment: There is no effective treatment.
G. Control: Once the disease is recognized, elimination of all rabbits in the colony has been the only effective way of preventing perpetuation of the infection. The disease should be reported to the state veterinarian and the USDA. Frozen carcasses may be saved for disease confirmation. Killed virus vaccines provide protection of naive rabbits exposed to the disease.