title: Molecular determinants of HIV-2 R5-X4 tropism in the V3 loop: development of a new genotypic tool.
abstract: OBJECTIVE
  The use of CCR5 inhibitors requires a tool to predict human immunodeficiency virus type 2 (HIV-2) tropism, as established in HIV-1. The aim of our study was to identify genotypic determinants of HIV-2 tropism located in the gp105 V3 loop.
  
  
  METHODS
  HIV-2 tropism phenotypic assays were performed on 53 HIV-2 clinical isolates using GFP expressing human osteosarcoma T4 [GHOST(3)] cell lines expressing CD4 and CCR5 or CXCR4 coreceptors. The gp105 V3 loop was sequenced and analyzed.
  
  
  RESULTS
  Thirty-four HIV-2 isolates were classified as R5, 7 as X4, and 12 as X4/R5 (dual). Substitution at residue 18 was always associated with a dual/X4 tropism (P < .00001). The following determinants were associated with dual/X4 tropism: a global net charge of more than +6 (P < .00001), V19K/R mutation (P < .00001), S22A/F/Y mutation (P < .002), Q23R mutation (P < .00001), and insertions at residue 24 (P < .00001), I25L/Y (P < .0004), R28K (P < .0004), and R30K (P < .014). These mutations were not found in R5 isolates, except R28K and R30K, which were detected in 4 and 5 R5 isolates, respectively. The 4 major genotypic determinants of dual/X4 tropism were mutation at residue 18, V19 K/R mutation, insertions at residue 24, and V3 global net charge.
  
  
  CONCLUSIONS
  We established a strong association between HIV-2 phenotypic tropism and V3-loop sequences, allowing for the prediction of R5- and/or X4-tropic viruses in HIV-2 infection.
authors.affiliation: Laboratoire de Virologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat-Claude Bernard, France.
authors.forename: Benoit
authors.initials: B
authors.lastname: Visseaux
authors.forename: Margarita
authors.initials: M
authors.lastname: Hurtado-Nedelec
authors.forename: Charlotte
authors.initials: C
authors.lastname: Charpentier
authors.forename: Gilles
authors.initials: G
authors.lastname: Collin
authors.forename: Alexandre
authors.initials: A
authors.lastname: Storto
authors.forename: Sophie
authors.initials: S
authors.lastname: Matheron
authors.forename: Lucile
authors.initials: L
authors.lastname: Larrouy
authors.forename: Florence
authors.initials: F
authors.lastname: Damond
authors.forename: Françoise
authors.initials: F
authors.lastname: Brun-Vézinet
authors.forename: Diane
authors.initials: D
authors.lastname: Descamps
mesh_terms: D001483:Base Sequence; D045744:Cell Line, Tumor; D056726:Genetic Association Studies; D060005:Genotyping Techniques / Q000379:methods*; D015498:HIV-2 / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D012367:RNA, Viral / Q000737:chemistry; D017423:Sequence Analysis, RNA; D056189:Viral Tropism / Q000235:genetics*; D054299:env Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D012367:RNA, Viral; D054299:env Gene Products, Human Immunodeficiency Virus; C069790:gp105 envelope protein, Human immunodeficiency virus 2