HIV XENOTRANSPLANTED NUDE MOUSE--ANTIVIRAL ASSAY MODEL

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The Human immunodeficiency virus (HIV) is the etiological agent of AIDS. To date there are only two FDA approved drugs which provide direct antiviral activity against this virus, and both toxicities and emerging resistance limit their widespread utility. In order for new and efficacious anti-HIV agent to enter human clinical trials, small animal models are required to demonstrate in vivo activity. Since HIV is a uniquely human virus, novel means are required to introduce this virus into rodent hosts. One such means is through the xenotransplantation of human HIV permissive cells into sublethally irradiated athymic mice. The P.I. of this proposal has previously demonstrated that the CEM cell line infected with the III-B strain of the HIV can reproducibly demonstrate high levels of p24 antigenemia using this novel approach. With anticipation of expanding this model into a fully accepted and valid small animal model of HIV infection for efficacy evaluation of pharmaceutical compounds, it is the overall objective of this proposal to continue to refine this model. This will be accomplished be expanding the transplantation aspect to include HIV permissive cells of various phenotypes; by expanding the HIV strains (including AZT resistant & primary) capable of replication within this system, and by introducing other well established means of measuring viral infectivity (i.e., FACS analysis). This additional information will provide a firm basis to design the experiments required for drug therapy determinations in this animal model system.