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Bioinformatics. 2013 Feb 15;29(4):451-60. doi: 10.1093/bioinformatics/btt002. Epub 2013 Jan 6.

Detecting and understanding genetic and structural features in HIV-1 B subtype V3 underlying HIV-1 co-receptor usage.

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  • 1Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.

Abstract

MOTIVATION:

To define V3 genetic elements and structural features underlying different HIV-1 co-receptor usage in vivo.

RESULTS:

By probabilistically modeling mutations in the viruses isolated from HIV-1 B subtype patients, we present a unique statistical procedure that would first identify V3 determinants associated with the usage of different co-receptors cooperatively or independently, and then delineate the complicated interactions among mutations functioning cooperatively. We built a model based on dual usage of CXCR4 and CCR5 co-receptors. The molecular basis of our statistical predictions is further confirmed by phenotypic and molecular modeling analyses. Our results provide new insights on molecular basis of different HIV-1 co-receptor usage. This is critical to optimize the use of genotypic tropism testing in clinical practice and to obtain molecular-implication for design of vaccine and new entry-inhibitors.

PMID:
23297034
[PubMed - indexed for MEDLINE]
PMCID:
PMC3570207
Free PMC Article
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