Positioning of Positively Charged Residues in the V3 Loop Correlates with HIV Type 1 Syncytium-inducing Phenotype

Although the V3 loop of the envelope glycoprotein (gp120) plays a role in determining the phenotype, pathogenesis, and tropism of human immunodeficiency virus-1 (HIV-1), there has not been any consistent correlation between structure and phenotype. Theoretically determined structures of the V3 loop of gp120, from 20 different viral strains, 10 syncytium-inducing (SI) and 10 non-syncytium-inducing (NSI) phenotype, revealed that all V3 loops from SI phenotypic strains had at least two positively charged residues in close proximity, on the same face of the loop. All of the SI phenotypic V3 loop structures were capable of forming strong divalent electrostatic interactions with disulfated sugars. The ability to form this interaction may be a determinant of the phenotype, tropism, and pathogenicity of HIV-1 viral strains. This structural motif was absent in all V3 loops from viral strains with the NSI phenotype.