The goal of this project is to identify murine retroviral gene products that are expressed during development and their possible role in resistance to retrovirus-induced disease. Using a panel of monoclonal antibodies derived from mice undergoing graft-versus-host disease we have identified a viral gp70 in embryo cell cultures. This gp70 is serologically related to a group of pathogenic recombinant (dualtropic) viruses and appears to correlate precisely in mouse strain distribution with the Rmcf resistance gene. This gene has been identified in certain strains of mice which are resistant to some forms of retrovirus-induced leukemia and specifically confers resistance to replication of recombinant dualtropic viruses. We are currently carrying out genetic experiments to determine linkage between this endogenous viral sequence and the Rmcf locus on chromosome 5. In order to gain a better understanding of the possible role of these endogenous viral sequences in resistance to disease, we have carried out some basic studies on the mechanisms of virus attachment and penetration of host cells. The efficiency of infection was found to be optimal at pH 7.6 but was markedly inhibited at mildly acidic pH. This was in striking contrast to the strict acidic pH dependence of entry of many other RNA enveloped viruses. We found that although the virus adsorption step was insensitive to pH, the rate of virus penetration was markedly inhibited at pH less than 6.4. The post-adsorption pH-sensitive step was a fusion event which was found to have an optimum of pH 7.6. These observations suggest that some murine retroviruses may be unable to enter the cytosol from within acidified endosomes, a common route of entry among other RNA viruses. Our current efforts in this area are focused on the identification of a retroviral fusion protein and its function in virus entry.
