Immunologic dysfunction during viral oncogenesis. I. Nonspecific immunosuppression caused by malignant rabbit fibroma virus.

Malignant rabbit fibroma virus (MV) is a potent oncogenic poxvirus that produces a rapidly progressive syndrome of disseminated myxosarcoma, immunosuppression, and fatal gram-negative infection. MV is probably a recombinant between Shope fibroma virus (SFV) and rabbit myxoma virus, and is capable of preventing or aborting the in vitro proliferative responses of rabbit lymphocytes to B and T lymphocyte mitogens. Proliferative responses to sheep erythrocytes (SRBC) are similarly affected, although MV does not alter ongoing antibody responses to SRBC. Splenic lymphocytes from MV tumor-bearing rabbits suppress antibody and proliferative responses to SRBC when added to lymphocytes from SRBC-primed rabbits. Finally, lysates of cultured splenic lymphocytes from rabbits given MV suppress both proliferative and antibody-forming responses to SRBC. When MV is removed from these lysates by UV inactivation or by centrifugation, the suppressive activity remains. We therefore conclude that MV induces immunologic unresponsiveness in rabbits by at least two mechanisms. First, a direct suppressive effect of added virus on in vitro lymphocyte proliferation is seen. There is no effect in this situation if an antibody response is already in progress. Second, spleen cells exposed to MV in vivo produce one or more soluble factors capable of suppressing both proliferative and antibody responses of normal lymphocytes.