A NATURALLY-OCCURRING SINGLE BASIC-AMINO-ACID SUBSTITUTION IN THE V3 REGION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 ENV PROTEIN ALTERS THE CELLULAR HOST-RANGE AND ANTIGENIC STRUCTURE OF THE VIRUS

Human immunodeficiency virus type 1 circulates in vivo as a mixture of heterologous populations (quasispecies). We previously analyzed the q uasispecies of the third hypervariable region (V3) in the viral envelo pe glycoprotein gp120 in an infected individual and found that the spe cies with a basic amino acid substitution (lysine for aspartic acid) a t a particular position evolved and became a distinct population withi n a short period, followed by progression to the typical immunodeficie ncy stage (S. Oka et al., AIDS Res. Hum. Retroviruses 10:271-277, 1994 ). In the present study, we examined the biological significance of th is amino acid substitution by constructing recombinant viruses with sp ecific point mutations and comparing their replication capabilities in different cell types. The results demonstrated that the single basic amino acid substitution was sufficient to render a virus fully capable of replicating in human T-cell lines under certain conditions. With a n acidic amino acid at the position, the virus grew much less fast or did not grow at all in the T-cell lines. Viral neutralization assay an d peptide enzyme-linked immunosorbent assays further showed that this amino acid substitution resulted in different recognition by several o f the serum specimens from human immunodeficiency virus type 1-infecte d individuals and thus could alter the antigenic structure. An additio nal finding worthy of note was that at the terminal stage, the provira l sequences of peripheral blood mononuclear cells and the viral isolat es from them were without exception of the late type with the basic am ino acid substitution, whereas the early sequence without the substitu tion was retained as a major subset in the spleen. These results suppo rt the notion that basic amino acid substitutions in V3 are a strong p redictor of virus tropism and may be relevant to disease progression.