HIV TYPE-1 V3 VARIATION DYNAMICS IN-VIVO - LONG-TERM PERSISTENCE OF NON-SYNCYTIUM-INDUCING GENOTYPES AND TRANSIENT PRESENCE OF SYNCYTIUM-INDUCING GENOTYPES DURING THE COURSE OF PROGRESSIVE AIDS

We performed a population-based sequence analysis of the envelope V3 r egion of human immunodeficiency virus type 1 (HIV-1) in two infected h emophiliacs. The study was conducted over 6-9 years, extending from th e asymptomatic phase to AIDS, In both patients, serial analysis showed that the V3 population at the initial stage consisted exclusively of putative non-syncytium-inducing (NSI) genotypes, Several of these clon es continued to be present without change for many years until the ter minal stage and often represented the dominant species in the populati on at each time interval, On the other hand, syncytium-inducing (SI) g enotypes mere initially absent but appeared shortly before severe depl etion of CD4(+) T cells and their proportion in the population appeare d to correlate with the viral load. In sharp contrast to NSI genotypes , SI genotypes displayed a significantly shorter presence, Thus, rapid gross population changes were found in SI genotypes, which were parti cularly frequent in the asymptomatic phase and less frequent in the te rminal stage. Furthermore, the ratio of nonsynonymous nucleotide subst itutions per synonymous substitutions in the V3 region in SI genotypes was higher than the corresponding value of NSI genotypes and the phyl ogenetic tree analysis revealed that a longer branch length was observ ed in SI genotypes than in NSI genotypes, These results suggest that t here might be a stronger pressure for selection on SI viruses than on NSI viruses during the high CD4 counts on the contrary to the fact tha t emergence of SI genotypes was well correlated with the rapid decline of CD4 count.