CONSERVED V3 LOOP SEQUENCES AND TRANSMISSION OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1

The third variable region (V3) of the surface glycoprotein (gp120) of envelope sequence subtype B, type 1 human immunodeficiency virus (HIV-1-B), is highly variable among T cell line-adapted viruses and syncytium-inducing HIV-1-B isolates. Here we analyze the V3 region sequences from 93 individuals close to the time of seroconversion and show that the cysteine-bridged V3 loop, which also encompasses a major neutralizing determinant, is highly conserved, whereas sequences immediately surrounding the loop are similarly divergent in all HIV-1-B strains. Viruses with this conserved V3 loop have been reported to be more resistant to antibody-mediated neutralization than T cell-adapted viruses with divergent V3 sequences. We hypothesize, therefore, that on transmission from a donor to a recipient, virions inherently more resistant to neutralization by donor antibodies have a greater chance of initiating infection than those more sensitive to neutralization. This might explain the conservation of V3 early in infection and has implications for the design of HIV vaccines.