The genetic variability of human immunodeficiency virus type 1 (HIV-1) particularly in the envelope gene, presents problems in developing a widely effective vaccine. In addition, this variability helps to determine some of the biological properties of the virus, such as cellular host range, cytopathic potential and virulence. A continued area of interest has been to identify targets of neutralization and analyze how env variability affects their recognition by neutralizing antibodies. Several mutants generated in vitro have been characterized and define distinct groups of human neutralizing antibodies. All appear to be conformational. One broadly neutralizing group of antibodies is directed towards a conformational epitope that maps close to the CD4 binding site of gp120. The contribution of the V3 loop towards neutralization by natural antisera has been studied using viruses with chimeric envelopes. These studies have shown that with at least some natural sera, in contrast to hyperimmune sera, the V3 loop constitutes at least part of a neutralization epitope that is both conformational and broadly recognized. With some other sera, the V3 loop appears to affect conformational epitopes outside the V3 loop. The genetic drift that occurs within individuals over extended time periods has been studied and found to be equivalent to that seen between individuals from the same geographic area. Genotypes of virus populations have been obtained from Nigeria, Zaire, Taiwan and Russia. An HIV-1(IIIB) variant has been identified which can grow on epithelioid cells; the bag gene appears to be critical for this cellular host range phenotype.
