Virus-lymphocyte interactions during the course of immunosuppressive virus infection.

Malignant rabbit fibroma virus (MV) is a lymphocytotropic leporipoxvirus which produces profound immunological dysfunction and lethal fibromyxosarcoma. We examined virus recovery from splenic lymphocytes as a function of time after inoculation in vivo, and correlated this with both immunological function and expression of virus-induced host suppressor activity. MV was most abundant in lymphocytes obtained 4 days following inoculation. At that time, immune function was relatively normal and host suppressor activity was not observed. By 7 days after infection, when active host immunosuppressor functions were observed, virus recovery was decreased. Eleven days post-inoculation host immune function began to recover despite increasing virus-induced tumours and developing opportunistic infection. Simultaneously, MV was no longer recoverable from spleen cells. Spleen cells from day 11 tumour-bearing rabbits did not support MV replication as efficiently as did normal or day 4 or 7 splenic lymphocytes, but they did not alter the ability of MV to grow in the latter cells. By fluorescence examination and cytofluorography, splenic lymphocytes bearing MV antigens were abundant 7 days after infection but disappeared by 11 days. This was temporally related to production of neutralizing antibody to MV, and development of virus-specific lymphocyte proliferative activity. The composition of splenic lymphocytes changed as well: the normal ratio of about 1:1 for B and T cells changed to 1:2 by day 7, and then inverted to almost 2:1 by day 11. Rabbits infected with MV thus appear to recover their immune function, concurrently eliminate virus-infected lymphocytes, and elaborate high titres of neutralizing serum antibodies despite progressive infections and tumour development.