EVOLUTION OF SEQUENCES ENCODING THE PRINCIPAL NEUTRALIZATION EPITOPE OF HUMAN IMMUNODEFICIENCY VIRUS-1 IS HOST-DEPENDENT, RAPID, AND CONTINUOUS

The principal neutralization epitope of human immunodeficiency virus 1 is localized in the third variable (V3) domain of the external envelope and has been shown to bind isolate-specific antibodies. Therefore, the extent of variation within the nucleic acid sequence encoding this epitope was studied in DNA directly obtained from peripheral blood mononuclear cells of six children and their plasma donor. This revealed that the quasi-species distribution of sequences obtained after cloning varied from recipient to recipient and that the distance from the donor sequences increased over time. V3 nucleotide evolution rates averaged 9.5 × 10-3 per site per year for silent sites and 11.4 × 10-3 per site per year for nonsilent sites (vs. 9.7 and 9.8 × 10-3 per site per year for a control region 5′ adjacent to the V3 region) and, although individual differences were observed, did not correlate with the serum antigen levels or disease progression. Sequences of both the epitope coding region itself (V3) and the control region upstream diverted more from the donor sequence among children not progressing to AIDS than among children progressing to AIDS. The evolution of V3 sequences is apparently host dependent, rapid, and independent of the level of antigen expression.