Early dissemination rates of Friend murine leukaemia virus variants correlate with late pathogenesis

Abstract

FIS-2, a less oncogenic, immunosuppressive variant of the Friend murine leukaemia virus (F-MuLV), was used to explore whether the differences in biological features were related to early virus dissemination rates or sites of replication. We found that erythroblasts were the primary target cells for both F-MuLV and FIS-2, while B- and T-cells were infected later in the infection. Although FIS-2 replicated to similar titres as F-MuLV, we observed a delay in peak viraemia titre and in the number of virus-positive cells in bone marrow and spleen. Studies including the chimeric viruses RE3 (FIS-2LTR with a F-MuLV background) and RE4 (F-MuLV LTR with a FIS-2 background) indicated that the delay in dissemination was due to mutations in FIS-2 LTR. The kinetics for early virus replication correlated with previously reported mean latency time for virus-induced erythroleukaemia in mice inoculated as newborns and with the onset of immunosuppression in adult mice. In addition, F-MuLV-induced late immunosuppression coincided with signs of erythroleukaemia and persistent viraemia. FIS-2 induced a more moderate late immunosuppression without persistent viraemia or signs of erythroleukaemia. Overall, our findings indicated that early viral replication is a prognostic factor in murine retrovirus-induced pathogenesis.