Variability and immunogenicity of human immunodeficiency virus type 1 p24 gene quasispecies.
Despite the conserved nature of the human immunodeficiency virus type 1 (HIV-1) gag gene, multiple quasispecies of the p24 gene coexist in HIV-1-infected 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%, suggesting a host-specific evolution. Synonymous and nonsynonymous nucleotide changes were evenly distributed in the p24 gene, with 27 and 28%, respectively, located within host human leukocyte antigen class I recognition sites. This would suggest only a minor influence from the host cytotoxic T-cell response on the evolution of the p24 gene. The importance of minor variations within p24 was analyzed by designing DNA-based immunogens from two distinct p24 quasispecies genes simultaneously derived from one patient. In plasmid-immunized H-2(b), H-2(d), and H-2(k) haplotype mice, a clear influence from the host major histocompatibility complex was noted on the immune responses, fully consistent with those noted when a recombinant p24 protein is used as the immunogen. The two p24 DNA immunogens did not differ in their immunogenicity, indicating that the limited genetic variability (<1%) had little influence on the immune responses.
Iroegbu
J
J
Divisions of Clinical Virology, F68, Karolinska Institute, Huddinge University Hospital, S-141 86 Huddinge, Sweden.
Birk
M
M
Lazdina
U
U
Sönnerborg
A
A
Sällberg
M
M
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000328:Adult; D000818:Animals; D001665:Binding Sites / Q000276:immunology; D003001:Cloning, Molecular; D015967:Gene Expression Regulation, Viral / Q000276:immunology; D014644:Genetic Variation; D016655:HIV Core Protein p24 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008969:Molecular Sequence Data; D010802:Phylogeny; D010957:Plasmids; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D017386:Sequence Homology, Amino Acid; D012698:Serologic Tests; D013045:Species Specificity
D016655:HIV Core Protein p24; D015395:Histocompatibility Antigens Class I; D011994:Recombinant Proteins