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Molecular Determinants of HIV-2 R5-X4 Tropism in the V3 Loop: Development of a New Genotypic Tool
- Source :
- Journal of Infectious Diseases; Vol 205
- Publication Year :
- 2011
- Publisher :
- Oxford University Press (OUP), 2011.
-
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.
- Subjects :
- Genotyping Techniques
Molecular Sequence Data
V3 loop
Biology
medicine.disease_cause
CXCR4
Green fluorescent protein
03 medical and health sciences
Cell Line, Tumor
Genotype
medicine
Humans
Immunology and Allergy
Genetic Association Studies
Tropism
030304 developmental biology
0303 health sciences
Mutation
Base Sequence
Sequence Analysis, RNA
030306 microbiology
env Gene Products, Human Immunodeficiency Virus
virus diseases
Phenotype
Virology
Molecular biology
3. Good health
Viral Tropism
Infectious Diseases
Cell culture
HIV-2
RNA, Viral
Subjects
Details
- ISSN :
- 15376613 and 00221899
- Volume :
- 205
- Database :
- OpenAIRE
- Journal :
- Journal of Infectious Diseases
- Accession number :
- edsair.doi.dedup.....321cd23fabc511bd7b59470d626b07a3