Conflicting data have been published concerning the correlation between the length of the second variable region (V2) in the HIV-1 envelope and the biological phenotype of the virus. Here the V2 region length of primary HIV-1 isolates was compared with biological phenotype and coreceptor usage. The V2 region variation was determined by DNA fragment length analysis, virus biological phenotype by the MT-2 cell assay, and coreceptor usage by infection of U87.CD4 cells expressing CCR3, CCR5, or CXCR4. Ninety-three primary virus isolates from 40 patients were analyzed. This panel of viruses included sequential isolates obtained from patients who progressed to AIDS with or without a virus phenotypic switch. We found that NSI MT-2-negative isolates had significantly shorter V2 regions than SI MT-2-positive isolates. However, when V2 region lengths of viruses were analyzed in more detail, we observed that NSI isolates obtained from patients shortly before the phenotypic switch had V2 region lengths similar to those of SI isolates. V2 regions of NSI isolates obtained from patients who progressed to AIDS without a virus phenotypic switch had, in contrast, shorter V2 region than isolates obtained just before virus phenotypic switch. Coreceptor analysis revealed that CCR5-using (R5) isolates generally had shorter V2 regions than virus isolates with the ability to enter CXCR4-expressing cells. Moreover, no significant difference in V2 region length was observed between monotropic SI isolates, that is, X4 isolates, and multitropic SI isolates, that is, R3R5X4 or R5X4 isolates. Thus, we conclude that R5 NSI isolates obtained from patients with stable virus phenotype through the whole disease course display shorter V2 regions than isolates obtained from patients at switch of virus phenotype, suggesting that V2 region length may influence virus coreceptor usage.
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