The major focus of this project has been on the genetic alteration of retroviruses as a result of recombination and point mutations. Such alterations generate mixed retroviral infections which are a hallmark of all in vivo retroviral infections. These include HIV and HTLV infections, which give rise to AIDS and T-cell leukemia in humans, and murine retrovirus infections which frequently result in proliferative, immunological or neurological diseases in mice. Our recent studies have investigated the effects of mixed in vivo retroviral infections after co-inoculation of mice with mixtures of murine leukemia viruses (MuLV). Infection by ecotropic MuLVs generally results in the de novo generation of polytropic MuLVs, which are recombinants between the inoculated ecotropic MuLV and endogenous polytropic MuLV envelope genes present in the genomes of inbred mice. The recombinant polytropic MuLVs, which have been implicated in pathogenicity, utilize a distinct cell-surface receptor and exhibit an infectious host range which differs from ecotropic MuLVs. We have found that infection of mice with mixtures of a polytropic MuLV and an ecotropic MuLV results in nearly complete suppression of de novo generation of polytropic MuLVs. Our results indicate that both viruses initially infect the same small population of cells of the monocyte/macrophage lineage and suggest that in vivo interference at this stage of infection may preclude further infectious spread of viruses. Further studies will determine if the small cell population is the initial target for other types of retroviruses and investigate if infection of this cell is a prerequisite for efficient infection of the mouse.
