Length variation of glycoprotein 120 V2 region in relation to biological phenotypes and coreceptor usage of primary HIV type 1 isolates

Conflicting data have been published concerning the correlation between the length of the second variable region (V2) in the HIV-1 envelope and the bi ological 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 b iological phenotype by the MT-2 cell assay, and coreceptor usage by infecti on of U87.CD4 cells expressing CCR3, CCR5, or CXCR4. Ninety-three primary v irus isolates from 40 patients were analyzed. This panel of viruses include d sequential isolates obtained from patients who progressed to AIDS with or without a virus phenotypic switch. We found that NSI MT-2-negative isolate s had significantly shorter V2 regions than SI MT-2-positive isolates. Howe ver, when V2 region lengths of viruses were analyzed in more detail, we obs erved that NSI isolates obtained from patients shortly before the phenotypi c 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 vir us phenotypic switch had, in contrast, shorter V2 region than isolates obta ined just before virus phenotypic switch. Coreceptor analysis revealed that CCR5-using (R5) isolates generally had shorter V2 regions than virus isola tes with the ability to enter CXCR4-expressing cells. Moreover, no signific ant difference in V2 region length was observed between monotropic SI isola tes, that is, X4 isolates, and multitropic SI isolates, that is, R3R5X4 or R5X4 isolates. Thus, we conclude that R5 NSI isolates obtained from patient s with stable virus phenotype through the whole disease course display shor ter V2 regions than isolates obtained from patients at switch of virus phen otype, suggesting that V2 region length may influence virus coreceptor usag e.