PATHOBIOLOGY OF RETROVIRUSES

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Simian immunodeficiency viruses (SIV) have recently been established as perhaps the most valuable tool for understanding immunopathogenic and molecular mechanisms of HIV-induced AIDS in people. Inoculation of rhesus macaques with SIVs derived from colony bred macaques and mangabeys results in varying degrees of retroviral induced AIDS-related disorders. Originally thought to be a homogeneous group of related SIVs, evidence now suggests that green monkeys harbor viruses which are genetically distinct from SIVs of macaques and mangabeys. The African green monkey is represented by phenotypically related races (subspecies) separated into distinct regions in sub-saharan Africa. In turn, phenotypically distinct SIVs have been isolated from two East African races (vervets and grivets) and are designated SIVver and SIVgri. This proposal will focus on the relationship of these viruses and newly identified viruses from West African subspecies of green monkeys to known HIV/SIVs. Viruses will be isolated, molecularly and antigenically characterized, and analyzed for biological and pathogenic diversity. Both biological and transfection-derived viral isolates from SIVagms will be examined in rhesus monkeys and green monkeys to better understand molecular and biologic variations related to pathogenesis and host resistance and susceptibility to disease. The specific aims are: 1) to isolate and characterize SIVs from naturally infected East and West African green monkeys; 2) to define distinguishing biological properties of SIVagms; and 3) to define the pathogenic mechanisms of SIVagms related to SIV/HIVs. The results of this project should provide valuable information in defining the pathogenic potential of genetically diverse SIVs and further will aid in understanding the mechanisms of viral and host determinants of AIDS. In addition, these studies will be important in understanding immune mechanisms for developing vaccine strategies for AIDS.