INTRAPATIENT SEQUENCE VARIATION OF THE GAG GENE OF HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 PLASMA VIRIONS

Because certain regions of the gag gene, such as p24, are highly conse rved among human immunodeficiency virus (HIV) isolates, many therapeut ic strategies have been directed at gag gene targets, Although intrapa tient variation of segments of gag have been determined, little is kno wn about the variability of the full-length gag gene for HIV isolated from a single individual, To evaluate intrapatient full-length gag var iability, we derived the nucleotide sequences of at least 10 cDNA gag clones of virion RNA isolated from plasma for each of four asymptomati c HIV type 1-infected patients with relatively high CD4(+) T-cell coun ts (300 to 450 cells per mm(3)). Mean values of intrapatient gag nucle otide variation obtained by pairwise comparisons ranged from 0.55 to 2 .86%. For three subjects, this value was equivalent to that reported f or intrapatient full-length env variation. The greatest range of intra patient mean nucleotide variation for individual protein-coding region s was observed for p7. We did not detect any G-to-A hypermutation, as A-to-G and G-to-A transitions occurred at similar frequencies, account ing for 29 and 25%, respectively, of the changes. Mean variation value s and phylogenetic analysis suggested that the extent of nucleotide va riation correlated with the length of viral infection, Furthermore, no distinct subpopulations of quasispecies were detectable within an ind ividual, The predicted amino acid sequences indicated that there were no regions within a gag protein that were comprised of clustered chang es.