Variability and immunogenicity of human immunodeficiency virus type 1 p24 gene quasispecies

Despite the conserved nature of the human immunodeficiency virus type I (HI V-1) gag gene, multiple quasispecies of the p24 gene coexist in HIV-1-infec ted patients. We cloned and sequenced 31 p24 genes from four HIV-1-infected patients. The intrapatient homology between the p24 genes ranged from 97.1 to 99.1%, whereas the interpatient homology ranged from 91.5 to 93.8%, sug gesting a host-specific evolution. Synonymous and nonsynonymous nucleotide changes were evenly distributed in the p24 gene, with 27 and 28%, respectiv ely, located within host human leukocyte antigen class I recognition sites, This would suggest only a minor influence from the host cytotoxic T cell r esponse on the evolution of the p24 gene. The importance of minor variation s within p24 was analyzed by designing DNA-based immunogens from two distin ct p24 quasispecies genes simultaneously derived from one patient. In plasm id-immunized H-2(b), H-2(d), and H-2(k) haplotype mice, a clear influence f rom the host major histocompatibility complex was noted on the immune respo nses, fully consistent with those noted when a recombinant p24 protein is u sed as the immunogen, The two p24 DNA immunogens did not differ in their im munogenicity, indicating that the limited genetic variability (<1%) had lit tle influence on the immune responses.