Mutational pathways and genetic barriers to CXCR4-mediated entry by human immunodeficiency virus type 1.

ABSTRACT: To examine mutational pathways that lead to CXCR4 use of HIV-1, we analyzed the genotypic and phenotypic characteristics of envelope sequences from a large panel of patient virus populations and individual clones containing different V3 mutations. Basic amino acid substitutions at position 11 were strong determinants of CXCR4-mediated entry but required multiple compensatory mutations to overcome associated reductions in infectivity. In contrast, basic amino acid substitutions at position 25, or substitutions at positions 6-8 resulting in the loss of a potential N-linked glycosylation site, contributed to CXCR4-mediated entry but required additional substitutions acting cooperatively to confer efficient CXCR4 use. Our assumptions, based upon examination of patient viruses, were largely con

SUBMITTER: Huang W 

PROVIDER: S-EPMC3428208 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature