INDEPENDENT VARIATION AND POSITIVE SELECTION IN ENV V1 AND V2 DOMAINSWITHIN MATERNAL-INFANT STRAINS OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1INVIVO

Multiple targets for immune recognition and cellular tropism are local ized to the V1 and V2 hypervariable regions in the amino portion of hu man immunodeficiency virus type 1 (HIV-1) gp120env. We have assessed g enetic diversity in env V1 and V2 hypervariable domains in vivo within epidemiologically related strains of HIV-1. Our strategy was to analy ze longitudinal samples from two seropositive mothers and multiple chi ldren infected by perinatal transmission. Although the V1 and V2 domai ns are closely linked in the HIV-1 genome, nucleotide sequences in V1 and in V2 evolved independently in maternal-infant viruses in vivo. A high proportion of the nucleotide substitutions would introduce amino acid diversity in V1 and in V2. A significant excess of nonsynonymous over synonymous substitutions was identified in HIV-1 env V1 and V2 pe ptides in the mothers and in two older children but was not generally apparent in HIV-1 sequences in infants. An excess of nonsynonymous ove r synonymous substitutions indicated that there is positive selection for independent genetic variation in the V1 and V2 domains in vivo. It is likely that there are host responses to complex determinants in th e V1 or V2 hypervariable domain of HIV-1 gp120.