Hamster Polyoma Virus Infection: Transmissible Lymphoma

Hamster polyoma virus (HaPyV) is a polyomavirus that is structurally and biologically similar to polyoma virus of mice, but is a distinctly different virus (see Mouse Chapter 1, "Polyomavirus Infections”).

Epizootiology and Pathogenesis

HaPyV is not common in laboratory hamsters, but may be found in some sources of pet hamsters. Infections of Syrian hamster colonies have been reported on several occasions in the United States and Europe. HaPyV is probably one of few truly hamster-origin viral agents, but its atypical virulence in Syrian hamsters is probably due to xenogeneic infection among distantly related hamster genera. It was probably introduced to laboratory Syrian hamsters in Eastern Europe through acquisition of wild European hamster (C. cricetus) stocks and mixing with laboratory Syrian hamsters. Natural latent infection, with isolation of virus from spleen and kidney tissue of subclinically infected European hamsters has been docu­mented, suggesting that the European hamster is the natural host. HaPyV causes multisystemic persistent infection with shedding in the urine, which may be subclinical. HaPyV is also oncogenic, but tumor forma­tion is a side effect of infection and not critical to the virus life cycle. HaPyV infection can result in the formation of lymphomas and hair follicle epitheliomas in hamsters.

With the above brief synopsis, the epizootiology of HaPyV can be understood. When first introduced to a naive population of breeding hamsters, HaPyV may result in epizootics of lymphoma, with attack rates as high as 80% among young hamsters within 4-30 weeks postexposure. Infected hamsters may also have a varia­ble incidence of trichoepitheliomas, usually around the face and feet, but they may arise anywhere on the body. Although the epitheliomas contain infectious virus, they are not necessary for virus transmission, which occurs primarily through the urine. Lymphomas do not con­tain infectious HaPyV, but HaPyV nucleic acid can be detected in their genome. Type C retrovirus particles (so- called hamster leukemia virus) also occur in these tumors, as they do in other tumors and normal tissues as an incidental finding. Once HaPV becomes enzootic, the incidence of lymphoma declines because young hamsters are presumably protected from infection by maternal antibody. In the enzootic context, the virus infects only older hamsters, which tend to resist the oncogenic effects. Infection of older hamsters often results in a clinically silent infection with persistent viruria. Enzootically infected hamsters, however, tend to develop a higher incidence of HaPyV skin tumors than do hamsters during the epizootic form, which develop lymphoma. These complex features have led to consid­erable confusion as to the etiology of transmissible lymphoma, including claims that it is caused by a DNA viroid-like agent.

Pathology

Hamsters with HaPyV lymphoma appear thin, often with palpable masses in their abdomens. Lymphomas usually arise in the mesenteric lymph nodes (Fig. 3.5) and gut-associated lymphoid tissue without involve­ment of the spleen, but they can arise in axillary and cervical lymph nodes. Mesenteric masses typically involve the intestinal wall and lymph nodes, with

FIG. 3.5. Hamster polyomavirus induced lymphoma in a hamster. Note the enlarged mesenteric lymph node (arrow) in the abdominal cavity. Source: Besselsen et al. 1999. Reproduced with permission from American Association for Laboratory Animal Science.

FIG. 3.6. Multiple cutaneous nodules (trichoepitheliomas) in a hamster infected with hamster polyomavirus. Source: J. Simmons, Inside Diagnostic and Consulting, Pearland, TX. Reproduced with permission from J. Simmons.

necrosis of the central region. This may result in intesti­nal ulceration and hemorrhage during the early stages of oncogenesis within the gut-associated lymphoid tissue. Infiltration of liver, kidney, thymus, and other organs can also occur. Tumors vary cytologically. They are usually lymphoid, but erythroblastic, reticulosarcoma- tous, and myeloid types have also been described. Lymphoid tumors are variably differentiated, usually immature, although sometimes they have plasmacytoid features. Lymphomas of the abdomen have been shown to possess B cell markers, and those of the thymus possess T cell markers. Affected hamsters may also pres­ent few to many nodular masses involving skin (Fig. 3.6). These lesions consist of keratinizing follicular structures reminiscent of trichoepitheliomas (Fig. 3.7).

FIG.

Diagnosis

Epizootic HaPyV is unmistakable. Lymphoid tumors are otherwise rare in hamsters, and when they occur, it is usually in aged hamsters. As stated earlier, virus isolation or electron microscopy of lymphoid tumors in an effort to find HaPyV is a vacuous exercise. Trichoepitheliomas have not been described in hamsters unless associated with HaPyV. If present, they offer the opportunity to visualize HaPyV crystalloids in the nucleus of keratiniz­ing epithelial cells, but only in that cell layer. A serologi­cal test for this virus is available, but it is generally not used routinely, and PCR amplification of HaPyV DNA is highly effective. Differential diagnoses must include transmissible ileal hyperplasia, which can cause palpable enlargement of the terminal ileum, spontaneous lymph­oid tumors, and skin lesions such as Demodex folliculitis.