CONSISTENT RISK GROUP-ASSOCIATED DIFFERENCES IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 VPR, VPU AND V3 SEQUENCES DESPITE INDEPENDENT EVOLUTION

Human immunodeficiency virus type 1 vpr, vpu and V3 sequences from 15 homosexual men and 19 intravenous drug users in the Amsterdam Cohort s tudies were analysed. Previously, we reported that V3 domains of virus es from drug users are distinguishable from those of homosexual men on the basis of two silent mutations. Phylogenetic analysis of vpr, vpu and V3 shows that differences in all three regions correlate with risk group. Two positions in both vpr and vpu were found to differ signifi cantly between the risk groups. The distinguishing positions were conf irmed for sequences from 11 Scottish and four German samples. The thre e regions show relatively independent evolution patterns; they resulte d in different phylogenies, the only stable clustering being that base d on the risk group distinction. Pairwise differences between sequence s of the genes were moderately correlated (around 0.30). Surprisingly, when only silent changes were counted, the correlations dropped almos t to zero, indicating that the evolution towards independence was more advanced in the silent than in the non-silent positions. This suggest s that selection at the amino acid level is not the primary driving fo rce for the independent evolutionary behaviour of the genes. Recombina tion, combined with restrictions on certain amino acids because of epi static interactions between the genes, could be an alternative explana tion of this phenomenon.