The primary tumors caused by leporipoxviruses in Sylvilagus rabbits, squirrels and hares all closely resemble proliférant fibromas. Following inoculation, an acute inflammatory reaction occurs with infiltration of polymorphonuclear and mononuclear cells and proliferation of fibroblast-like cells of uncertain origin. The 'tumor' consists of pleomorphic cells imbedded in a matrix of intercellular fibrils of collagen. Unlike the transformed cells induced by other DNA tumor viruses, cells from poxviral tumors are not immortalized and, cannot be propagated independently. Instead they appear to require secreted virus-encodèd proteins in order to sustain the hyperproliferative state. Inclusion bodies characteristic of poxviral replication can be observed in the cytoplasms of epithelial and some fibroma cells. As the tumor develops, mononuclear leukocyte cuffing of adjacent vessels is observed and at the base of the tumor there is accumulation of lymphocytes, plasma cells, macrophages and neutrophils. The ratio between influx of inflammatory cells and fibroblast proliferation is variable but generally there is little or no necrosis. The speed with which immune cells clear the viral infection and reverse the hyperproliferation can range from 1—2 weeks up to 6 months, depending on both the virus and the host.
The principal difference between the benign fibroma syndrome described above and the devastating disease caused by MYX in Oryctolagus rabbits is that the latter viruses efficiently propagate in host lymphocytes and are able to circumvent the cell-mediated immune response to the viral infection. The subcutaneous tumors consist of proliferating undifferentiated mesenchymal cells which become large and stellate with prominent nuclei ('myxoma' cells). In surrounding tissue there can be extensive proliferation of endothelial cells of the local capillaries and venules, often to the point where complete occlusion leads to extensive necrosis of the infected site. The overlying epithelial cells can show hyperplasia or degeneration, depending on the virus strain, and poxviral inclusion bodies are frequently observed in the prickle-cell layer. In some MYX strains primary and secondary skin tumors can undergo extensive hemorrhage and internal lesions may be found in the stomach, intestines and heart. The virus readily migrates to secondary sites within infected immune cells and concomitant cellular proliferation can be detected in the reticulum cells of lymph nodes and spleen, as well as the conjunctival and pulmonary alveolar epithelium. The nasal mucosa and conjunctiva overlying secondary tumors undergo squamous metaplasia such that the epithelia become nonciliated and nonkeratizing. Disruption of the ciliary architecture may be one of the factors which facilitate the extensive Gram-negative bacterial infections of the eyes, nose and respiratory tract. Varying degrees of inflammatory cell infiltration by polymorphonuclear heterophils occur soon after infection but there is only a limited effective cellular immune response. The lymph nodes and spleen show evidence of aberrant T-cell activation and hyperplasia and infectious virus can be isolated from all lymphoid organs except the thymus. Death is believed to be caused by a combination of tissue damage from the increasing tumor burden, generalized immunosuppression and debilitating bacterial colonization of the respiratory tract.
Little is known about SPV pathogenesis but gross features closely resemble those of the noninvasive orthopoxviruses in their native hosts.
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