ROLE OF V1V2 IN HIV TENASMISSION AND PATHOGENESIS

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. To study heterosexual transmission of HIV-1, we have analyzed the genotypic and phenotypic characteristics of viruses transmitted between partners enrolled in a large HIV-discordant couple cohort in Zambia (The Zambia-Emory HIV Research Project). We have characterized over 200 viral Env proteins derived from eight donor-recipient transmission pairs, and have found that transmission consistently selects for a compact, neutralization-sensitive variant of the HIV-1 surface glycoprotein, gp120. We are currently extending these studies to investigate the nature of this strong selection on the env gene during transmission and to understand how the Env glycoproteins evolve from early infection into chronic disease. Information provided from these studies will also be used to design Env-based vaccine immunogens targeted at eliciting a potent neutralizing antibody response.