HIV Type 1 V3 Variation Dynamicsin Vivo: Long-Term Persistence of Non-Syncytium-Inducing Genotypes and Transient Presence of Syncytium-Inducing Genotypes during the Course of Progressive AIDS

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Abstract
We performed a population-based sequence analysis of the envelope V3 region of human immunodeficiency virus type 1 (HIV-1) in two infected hemophiliacs. The study was conducted over 6-9 years, extending from the 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 clones continued to be present without change for many years until the terminal stage and often represented the dominant species in the population at each time interval. On the other hand, syncytium-inducing (SI) genotypes were initially absent but appeared shortly before severe depletion of CD4+ T cells and their proportion in the population appeared 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 particularly frequent in the asymptomatic phase and less frequent in the terminal stage. Furthermore, the ratio of nonsynonymous nucleotide substitutions per synonymous substitutions in the V3 region in SI genotypes was higher than the corresponding value of NSI genotypes and the phylogenetic tree analysis revealed that a longer branch length was observed in SI genotypes than in NSI genotypes. These results suggest that there 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 that emergence of SI genotypes was well correlated with the rapid decline of CD4 count.