Evolutionary mechanisms and population dynamics of the third variable envelope region of HIV within single hosts.

Clonal diversifications of HIV virus were monitored by periodic samplings on each of the six patients with regard to 183- to 335-bp segments of the env gene, which invariably included the functionally critical V3 region. Subsequently, six individual phylogenetic trees of viral variants were constructed. It was found that at one time or another during the course of disease progression, viral variants were inexplicably released from a strong negative selection against nonsynonymous base substitutions, possibly indicating positive selection. This resulted in concentrated amino acid substitutions at five specific sites within the V3 region. It was noted that these sites were often involved as antigenic determinants that provoked the host immune response and that these sites were also involved in the determination of viral phenotypes as to their cell tropism, syncytium formation capability, and replication rates.