Foamy viruses are complex retroviruses with replication pathways which differ greatly from those of the conventional retroviruses such as oncoviruses or lentiviruses. The prototype foamy virus is HFV, which was isolated from a human cell line, but which is virtually identical to a chimpanzee virus. Foamy viruses are not prevalent in human populations, but humans can be infected through contact with primates. The course of infection by HFV and other foamy viruses is distinct from that of the other retroviral genera in that a life long, persistent, apparently benign, infection ensues. Virus can often be isolated decades after initial infection. This is true for both natural hosts, such as primates, cats or cows, and accidentally infected hosts such as humans. In vitro, HFV is highly cytopathic in some cell types, yet persistent infection ran be obtained in other cells. Little is known about the difference in host cell response. The goal of this proposal is to use both permissive and persistent cells in culture, and a mouse model to dissect the contributions of viral gene products and the host immune system in establishment of benign persistent infections. Immune competent mice can be infected with HFV without ensuing pathology.
Three specific aims are proposed. 1. To characterize HFV infections in vitro in a variety of cell lines and normal cell types. These experiments will define the host range of the virus, including the cell types in which virus can integrate. 2. To determine the role of the viral non-structural protein Bet, as well as that of the two viral promoters in the outcome of infection (persistent vs. permissive). 3. To characterize of the host immune response to the virus. In vitro assays will be used to study T cell responses to viral infection. The course and ultimate outcome of infection in wt and immune deficient mice will be assessed. This set of experiments should help determine whether the absence of pathogenicity in normal animals is a function of the viral replication pathway, specific host defenses, or both. These experiments will be will be important for the assessment of the utility of foamy viruses as vectors for gene therapy.
