CONVERGENT EVOLUTION WITHIN THE V3 LOOP DOMAIN OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 IN ASSOCIATION WITH DISEASE PROGRESSION

Phylogenetic analysis was used to study in vivo genetic variation of t he V3 region of human immunodeficiency virus type 1 in relation to dis ease progression in six infants with vertically acquired human immuno deficiency virus type 1 infection. Nucleotide sequences from each infa nt formed a monophyletic group with similar average branch lengths sep arating the sets of sequences. In contrast to the star-shaped phylogen y characteristic of interinfant viral evolution, the shape of the phyl ogeny formed by sequences froth the infants who developed AIDS tended to be linear. A computer program, DISTRATE, was written to analyze cha nges in DNA distance values over time. For the six infants, the rate o f divergence from the initial variant was inversely correlated with CD 4 cell counts averaged over the first 11 to 15 months of life (r = -0. 87, P = 0.024). To uncover evolutionary relationships that might be di ctated by protein structure and function, tree-building methods were a pplied to inferred amino acid sequences, Trees constructed from the fu ll-length protein fragment (92 amino acids) showed that viruses from e ach infant formed a monophyletic group. Unexpectedly V3 loop protein s equences (35 amino acids) that were found at later time points from th e two infants who developed AIDS clustered together Furthermore; these sequences uniquely shared amino acids that have been shown to confer a T-cell line tropic phenotype. The evolutionary pattern suggests that viruses from these infants with AIDS acquired similar and possibly mo re virulent phenotypes.