title: HIV-2 A-subtype gp125c₂-v₃-c₃ mutations and their association with CCR5 and CXCR4 tropism.
abstract: The early events of the HIV replication cycle involve the interaction between viral envelope glycoproteins and their cellular CD4-chemokine (CCR5/CXCR4) receptor complex. In this study, for the first time, the HIV-2 A-subtype gp125(C2-V3-C3) mutations and their tropism association were characterized by analyzing 149 HIV-2 sequences from the Los Alamos database. The analysis has strengthened the importance of C2-V3-C3 region as a determinant factor for co-receptor selection. Moreover, statistically significant correlations were observed between C2-V3-C3 mutations, and several correlated mutations were associated with CXCR4 and CCR5 co-receptor usage. A dendrogram showed two distinct clusters, with numerous associated mutations grouped, thus dividing CCR5- and CXCR4-tropic viruses. Fourteen X4-tropic virus mutations, all in V3 and C3 domains and forming highly significant subclusters, were found. Finally, R5 associations, two strong subclusters were observed, grouping several C2-V3-C3 mutated positions. These data indicate the possible contribution of C2-V3-C3 mutational patterns in regulating HIV-2 tropism.
authors.affiliation: Virology, Department of Experimental Medicine and Biochemistry, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Dimonte
authors.forename: Valentina
authors.initials: V
authors.lastname: Svicher
authors.forename: Romina
authors.initials: R
authors.lastname: Salpini
authors.forename: Francesca
authors.initials: F
authors.lastname: Ceccherini-Silberstein
authors.forename: Carlo-Federico
authors.initials: CF
authors.lastname: Perno
authors.forename: Muhammed
authors.initials: M
authors.lastname: Babakir-Mina
mesh_terms: D020816:Amino Acid Motifs; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism* / Q000821:virology; D015498:HIV-2 / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation; D011485:Protein Binding; D019713:Receptors, CCR5 / Q000235:genetics / Q000378:metabolism*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D056189:Viral Tropism; D054299:env Gene Products, Human Immunodeficiency Virus / Q000737:chemistry* / Q000235:genetics* / Q000378:metabolism
chemical_list: D019713:Receptors, CCR5; D019718:Receptors, CXCR4; D011991:Receptors, Virus; D054299:env Gene Products, Human Immunodeficiency Virus; C066316:gp125 envelope protein, Human immunodeficiency virus 2