SUPPRESSION OF RAT CYTOMEGALOVIRUS REPLICATION BY ANTIBODIES AGAINST GAMMA-INTERFERON

The role of gamma interferon (IFN-gamma) in the resolution of rat cyto megalovirus (RCMV) infection was investigated. In the spleen, IFN-gamm a-producing cells reached maximum numbers on day 7 after infection. Pr ophylactic treatment with high doses of recombinant rat IFN-gamma exer ted antiviral activity in fibroblasts and protected immunosuppressed r ats against a lethal RCMV challenge. Remarkably, in immunocompetent ra ts, neutralization of endogenous IFN-gamma activity significantly redu ced the numbers of RCMV antigen-expressing cells in the spleen, the pr edominant site of viral replication. Moreover, protection of radiation -immunosuppressed infected rats by transferred immune T cells was enha nced by coinjection of IFN-gamma neutralizing antibodies. The observat ions were paralleled by in vitro findings: low concentrations of IFN-g amma enhanced viral replication in both macrophages and fibroblasts. T hese data suggest that IFN-gamma can play different and even opposite roles in the regulation of RCMV replication in vivo; T lymphocytes may contribute to the progression of RCMV infection by secreting IFN-gamm a.