Multiple targets for immune recognition and cellular tropism are localized to the Vi and V2 hypervariable regions in the amino portion of human immunodeficiency virus type 1 (HIV-1) gpl20e'v. We have assessed genetic diversity in env Vl and V2 hypervariable domains in vivo within epidemiologically related strains of HIV-1. Our strategy was to analyze longitudinal samples from two seropositive mothers and multiple children infected by perinatal transmission. Although the Vi and V2 domains are

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... sely linked in the HIV-1 genome, nucleotide sequences in Vl and in V2 evolved independently in maternal-infant viruses in vivo. A high proportion of the nucleotide substitutions would introduce amino acid diversity in Vl and in V2. A significant excess of nonsynonymous over synonymous substitutions was identified in HIV-1 env Vl and V2 peptides in the mothers and in two older children but was not generally apparent in HIV-1 sequences in infants. An excess of nonsynonymous over synonymous substitutions indicated that there is positive selection for independent genetic variation in the Vl and V2 domains in vivo. It is likely that there are host responses to complex determinants in the Vi or V2 hypervariable domain of HIV-1 gpl20. tage is that the source of HIV-1 infection in the infant is unambiguous. Another is that evolution of genetic diversity in related strains of HIV-1 can be examined both in adults and in the context of the developing immune system of the 3951 on May 9, 2020 by guest