Naturally occurring variability in the envelope glycoprotein of HIV-1 and development of cell entry inhibitors.

ABSTRACT: Naturally occurring genetic variability across HIV-1 subtypes causes amino acid polymorphisms in encoded HIV-1 proteins including the envelope glycoproteins associated with viral entry. The effects of amino acid polymorphisms on the mechanism of HIV-1 entry into cells, a process initiated by the binding of the viral envelope glycoprotein gp120 to the cellular CD4 receptor, are largely unknown. In this study, we demonstrate that amino acid polymorphisms affect the structural stability and domain cooperativity of gp120 and that those differences are reflected in the binding mechanism of the viral envelope glycoprotein to the cell surface receptor and coreceptor. Moreover, subtype differences also affect the binding behavior of experimental HIV cell entry inhibitors. While gp120-A has a sligh

SUBMITTER: Brower ET 

PROVIDER: S-EPMC2840190 | biostudies-literature | 2010 Mar

REPOSITORIES: biostudies-literature