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.
OBJECTIVE: The use of CCR5 inhibitors requires a tool to predict humanimmunodeficiency 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 humanosteosarcoma 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: Selly Ba; Dana N Raugi; Robert A Smith; Fatima Sall; Khadim Faye; Stephen E Hawes; Papa Salif Sow; Moussa Seydi; Geoffrey S Gottlieb Journal: Clin Infect Dis Date: 2018-10-30 Impact factor: 9.079
Authors: Quirina Santos-Costa; Maria Manuel Lopes; Marta Calado; José Miguel Azevedo-Pereira Journal: Retrovirology Date: 2014-11-25 Impact factor: 4.602
Authors: Nicolas Cazals; Quentin Le Hingrat; Bruno Abraham; Patricia Da Silva; Laure Guindre; Sylvie Goffart; Florence Damond; Benoît Visseaux; Charlotte Charpentier; Sylvie Ranger-Rogez; Diane Descamps Journal: Open Forum Infect Dis Date: 2018-09-11 Impact factor: 3.835