Inhibition of virus replication does not alter malignant rabbit fibroma virus-induced immunosuppression

Malignant rabbit fibroma virus (MV) directly suppresses generation of antibody responses and mitogen induced T and B lymphocyte proliferation. We investigated whether this phenomenon required expression of the complete viral genome. Phosphonoacetic acid (PAA) inhibits poxvirus specific DNA polymerases. Adding PAA to cultures reduces both MV replication and mitogen-driven rabbit lymphocyte proliferation in a dose-dependent fashion. A dose of PAA adequate to inhibit MV replication by about 97%, but insufficient to reduce lymphocyte proliferation appreciably, does not affect the ability of MV to suppress lymphocyte proliferation or initiation of antibody production. Spleen cells from MV tumour-bearing rabbits contain very little virus, but inhibit the proliferative and antibody forming responses of normal spleen cells. This activity is shown here to reflect the production by T lymphocytes of a soluble mediator of greater than 25 kD molecular weight. Adding PAA to these mixed spleen cell cultures does not alter the ability of MV to induce T suppressor activity in host lymphocytes. Thus, these immunosuppressive capabilities of MV appear to reflect early MV gene functions.