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.
Detecting and understanding genetic and structural features in HIV-1 B subtype V3 underlying HIV-1 co-receptor usage / M. Chen, V. Svicher, A. Artese, G. Costa, C. Alteri, F. Ortuso, L. Parrotta, Y. Liu, C. Liu, C. Perno, S. Alcaro, J. Zhang. - In: BIOINFORMATICS. - ISSN 1367-4803. - 29:4(2013 Feb 15), pp. 451-460.
|Titolo:||Detecting and understanding genetic and structural features in HIV-1 B subtype V3 underlying HIV-1 co-receptor usage|
PERNO, CARLO FEDERICO (Corresponding)
|Settore Scientifico Disciplinare:||Settore MED/07 - Microbiologia e Microbiologia Clinica|
|Data di pubblicazione:||15-feb-2013|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1093/bioinformatics/btt002|
|Appare nelle tipologie:||01 - Articolo su periodico|