Host and Viral Factors in HIV Pathogenesis.

Texas Tech University Health Scis Center, Lubbock TX

Investigators

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Abstract

? DESCRIPTION (provided by applicant): HIV infection in humans leads to a progressive depletion of CD4+ T cells resulting in immunodeficiency. However, the mechanism by which HIV depletes CD4+ cells specifically remains one of the most important yet unanswered questions in AIDS research. Although HIV selectively infects CD4+ cells, the relatively few infected cells in vivo does not account for the extent of CD4+ T cell depletion. This has led to the idea that the virus is able to kill uninfected bystander CD4+ cells. Several viral and host associated factors have been proposed to play a role in the AIDS pathogenesis like the viral Env glycoprotein, immune activation, host CCR5 genotypic make-up etc. While HIV disease is clearly associated with immune activation and CD4+ T cell decline, the cause and consequence relation of the two has yet to be established. Moreover, the interaction of the viral Env glycoprotein with the host in regulating AIDS progression remains unknown. Hence, in this study, we propose to conduct a comprehensive examination of the host factors like immune activation, CCR5 gene and promoter polymorphism as well as viral determinant like phenotype and genotype of the Env genes derived from HIV-1 infected patients to determine how they play a concerted role in AIDS progression. Importantly, understanding the host and viral factors in disease progression may have diagnostic use for predicting disease outcome as well as developing treatment strategies.