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.
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.
Authors: Stefano Alcaro; Anna Artese; James N Iley; Sotiris Missailidis; Francesco Ortuso; Lucia Parrotta; Raffaele Pasceri; Francesco Paduano; Claudia Sissi; Francesco Trapasso; Maria Gabriella Vigorita Journal: ChemMedChem Date: 2010-04-06 Impact factor: 3.466
Authors: Christopher T Veldkamp; Christoph Seibert; Francis C Peterson; Norberto B De la Cruz; John C Haugner; Harihar Basnet; Thomas P Sakmar; Brian F Volkman Journal: Sci Signal Date: 2008-09-16 Impact factor: 8.192
Authors: Raphael W Lihana; Samoel A Khamadi; Raphael M Lwembe; Joyceline G Kinyua; Joseph K Muriuki; Nancy J Lagat; Fredrick A Okoth; Ernest P Makokha; Elijah M Songok Journal: BMC Infect Dis Date: 2009-12-30 Impact factor: 3.090
Authors: V C Di Maio; V Cento; C Mirabelli; A Artese; G Costa; S Alcaro; C F Perno; F Ceccherini-Silberstein Journal: Antimicrob Agents Chemother Date: 2014-03-03 Impact factor: 5.191