HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBTYPES DEFINED BY ENV SHOW HIGH-FREQUENCY OF RECOMBINANT GAG GENES

Genetic subtypes of human immunodeficiency virus type 1 can be disting uished on the basis of phylogenetic analysis of their envelope (env) g ene. A significant proportion of human immunodeficiency virus type 1 s trains was retrospectively shown to result from recombination events b etween viruses belonging genetically to distinct subtypes (D. L. Rober tson, P. M. Sharp, F. E. McCutchan, and B. H. Hahn, Nature [London] 37 4:124-126, 1995). To establish the frequency of natural infections wit h recombinant viruses and to exclude tissue culture artifacts, we anal yzed plasma samples from the UNAIDS sample collection. The collection includes samples from 53 individuals infected with subtype A (n = 9), subtype B (n = 15), subtype C (n = 1), subtype D (n = 13), and subtype E (n = 15) on the basis of V3 region analysis. Phylogenetic analysis of the gag gene fragment showed intersubtype recombinant genomes in 23 cases: 3 of 9 (33%) of subtype A, 2 of 15 (13%) of subtype B, 3 of 13 (23%) of subtype D, and all of subtype E. Of the 23 recombinant virus es, 19 had a gag gene from one subtype and env from another (B-env/C-g ag, A(env)/C-gag, D-env/A(gag), and E(env)/A(gag)). Phylogenetic analy sis clustered the A(gag) of subtype E viruses as an outgroup of subtyp e A, suggesting that these viruses may belong to a distinct A' cluster . The remaining four recombinant viruses (B-env/(BFp24)-F-p17, A(env)/ A(p17)D(p24), A(env)/A(p17)C(p24), and D-env/D(p17)A(p24)) had breakpo int crossover sites in the proximity of the p17-p24 protein processing site. We conclude that recombination in the gag gene is highly freque nt among the major ear subtypes and that selection of recombinants is apparently based on particularly beneficial combinations of gag and en v gene products.