GENETIC-DIFFERENCES BETWEEN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 SUBPOPULATIONS IN FECES AND SERUM

To study human immunodeficiency virus type 1 (HIV-1) compartmentalizat ion between intestine and blood, paired faecal and serum samples were collected from 204 HIV-l-infected persons. Direct sequencing of the gp 120 V3 region obtained from 33 persons showed that faecal and serum se quences could be nearly homologous (0.3% different) or very dissimilar (11.3% different). Individual clones were obtained and sequenced from the faecal and serum samples of 13 persons. In 6 persons the HIV-1 su bpopulations in faeces and serum were similar, whereas in 7 persons, d istribution of V3 genotypes showed a marked difference. Genetic charac terization of the HIV-1 subpopulations showed less heterogeneity in fa ecal subpopulations than in serum subpopulations in 5 of the 7 subject s, Furthermore, faecal and serum subpopulations differed predominantly by nonsynonymous nucleotide substitutions (in 6 of 7 persons). Compar ison of the HIV-1 subpopulations in faeces and serum of these 7 person s, using resampling techniques, revealed a significant difference betw een faecal and serum subpopulations at an N-linked glycosylation site, C-terminal of the V3 loop (amino acids 331-333), Sequences from faeca l subpopulations of all 7 persons contained a glycosyIation site at am ino acid position 331-333. Four of these 7 harboured serum variants la cking a glycosylation site at this position. The faecal subpopulations in these 4 persons showed limited nonsynonymous substitutions compare d to synonymous substitutions, indicating that purifying selection is operational on these subpopulations.