title: Detecting and understanding genetic and structural features in HIV-1 B subtype V3 underlying HIV-1 co-receptor usage.
abstract: BACKGROUND
  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.affiliation: Program of Computational Biology and Bioinformatics, Yale University, New Haven, CT 06520, USA.
authors.forename: Mengjie
authors.initials: M
authors.lastname: Chen
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Anna
authors.initials: A
authors.lastname: Artese
authors.forename: Giosuè
authors.initials: G
authors.lastname: Costa
authors.forename: Claudia
authors.initials: C
authors.lastname: Alteri
authors.forename: Francesco
authors.initials: F
authors.lastname: Ortuso
authors.forename: Lucia
authors.initials: L
authors.lastname: Parrotta
authors.forename: Yang
authors.initials: Y
authors.lastname: Liu
authors.forename: Chang
authors.initials: C
authors.lastname: Liu
authors.forename: Carlo Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Stefano
authors.initials: S
authors.lastname: Alcaro
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
mesh_terms: D005838:Genotype; D015699:HIV Envelope Protein gp120 / Q000737:chemistry / Q000235:genetics*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D006801:Humans; D015233:Models, Statistical; D062105:Molecular Docking Simulation; D009154:Mutation; D019713:Receptors, CCR5 / Q000737:chemistry*; D019718:Receptors, CXCR4 / Q000737:chemistry*
chemical_list: D015699:HIV Envelope Protein gp120; D019713:Receptors, CCR5; D019718:Receptors, CXCR4; C514793:gp120 protein, Human immunodeficiency virus 1