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


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

SUBMITTER: Chen M 

PROVIDER: S-EPMC3570207 | biostudies-literature | 2013 Feb

REPOSITORIES: biostudies-literature

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

Chen Mengjie M   Svicher Valentina V   Artese Anna A   Costa Giosuè G   Alteri Claudia C   Ortuso Francesco F   Parrotta Lucia L   Liu Yang Y   Liu Chang C   Perno Carlo Federico CF   Alcaro Stefano S   Zhang Jing J  

Bioinformatics (Oxford, England) 20130106 4


<h4>Motivation</h4>To define V3 genetic elements and structural features underlying different HIV-1 co-receptor usage in vivo.<h4>Results</h4>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 b  ...[more]

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