HOST-SPECIFIC DRIVING-FORCE IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 EVOLUTION IN-VIVO

To investigate the process of human immunodeficiency virus type 1 (HIV -I) evolution in vivo, a total of 179 HIV-1 V3 sequences derived from cell-free plasma were determined from serial samples in three epidemio logically linked individuals (one infected blood donor and two transfu sion recipients) over a maximum period of 8 years. A systematic analys is of pairwise comparisons of intrapatient sequences, both within and between each sample time point, revealed a preponderance and accumulat ion of nonsynonymous rather than synonymous substitutions in the V3 lo op and flanking regions as they diverged over time. This strongly argu es for the dominant role that positive selection for amino acid change plays in governing the pattern and process of HIV-1 env V3 evolution in vivo and nullifies hypotheses of purely neutral or mutation-driven evolution or completely chance events. In addition, different rates of evolution of HIV-1 were observed in these three different individuals infected with the same viral strain, suggesting that the degree of po sitive pressure for HIV-1 amino acid change is host dependent. Finally , the observed similar rate of accumulation in divergence within and b etween infected individuals suggests that the process of genetic diver gence in the HIV epidemic proceeds regardless of host-to-host transmis sion events, i.e., that transmission does not reset the evolutionary c lock.