CCR5 POLYMORPHISMS AND SUSCEPTIBILITY TO HIV 1 INFECTION
Scripps Research Institute, La Jolla CA
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Abstract
HIV-1 enters target cells by interacting with two cell surface receptors, CD4 and one of several chemokine receptors. The most common co-receptor is CCR5, and mutations in the CCR5 gene that prevent surface expression also block HIV-1 transmission. The level of CCR5 expression is highly variable between different individuals, and polymorphisms in the non-coding regions have been proposed to explain these differences. The specific aim of this proposal is to identify sequence polymorphisms upstream of the transcription start site in CCR5, and correlate these polymorphisms with levels of CCR5 expresion and susceptibility to HIV-1 infection. A second specific aim is to determine the effect of CCR5 antagonists on virus infection in individuals differing in CCR5 expression.
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