In this application, the authors seek to evaluate chimeric simian-human immunodeficiency virus (SHIV) infection of monkeys, which has been demonstrated to be applicable to studies aimed at examining the impact of env variation and viral replication and pathogenesis in vivo. The investigators have derived a pathogenic SHIV, 33A, a model system for testing the in vivo relevance of in vitro differential viral replication and cytopathicity, to identify the genetic determinants of HIV-1 pathogenesis in vivo and to screen the efficacy of envelope- based vaccines in protection from disease progression. The investigators propose to use both biologic and genetic approaches to: (1) establish the in vitro correlates of SHIV pathogenesis in vivo and 92) to generate a pathogenic SHIV33A clone for identification of sequence changes that correlate with changes in vitro biologic and serological properties and in vivo viral pathogenesis. As well, pathogenic envelope SHIV, which resembles more closely the properties of a primary HIV-1 isolate in terms of co-receptors usage and envelope antigenic structure, is proposed to be constructed.
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