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

作者：Chen Mengjie; Svicher Valentina; Artese Anna; Costa Giosue; Alteri Claudia; Ortuso Francesco; Parrotta Lucia; Liu Yang; Liu Chang; Perno Carlo Federico^*; Alcaro Stefano; Zhang Jing

来源：Bioinformatics, 2013, 29(4): 451-460.

DOI：10.1093/bioinformatics/btt002

Motivation: To define V3 genetic elements and structural features underlying different HIV-1 co-receptor usage in vivo. %26lt;br%26gt;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.

• 出版日期2013-2-15