Nonsynonymous mutations within the human immunodeficiency virus type 1 p17 gene are clustered to sequences binding to the host human leukocyte antigen class I molecules

We have analyzed the relation between intrapatient variabilities of the p17 gene and the location of known host p17 cytotoxic T lymphocyte (CTL) epitopes in five patients infected with human immunodeficiency virus type 1 (HIV-1), All patients were typed with respect to the human leukocyte antigen (HLA) class I type, One to seven previously fine-mapped p17 CTL epitopes corresponded to the HLA class I restriction elements of each patient, An average of 28 +/- 16% of the p17 gene of each patient encoded CTL epitopes corresponding to the HLA restriction elements of the host, Twenty full-length p17 gene clones were sequenced from each patient, The intrapatient homology between the p17 sequences ranged from 96.4 to 98.9%, The interpatient homology between the consensus sequences of each patient ranged from 83.1 to 91.6%, A total of 246 nucleotide differences within the 100 p17 clones was noted, Fifteen (16%) of 96 synonymous substitutions mere found within host CTL epitopes, whereas 72 (48%) of 150 nonsynonymous nucleotide changes were found within CTL epitopes corresponding to the HLA restriction elements of the host (p < 0.0001; Fisher's exact test), Subsequently, variable residues indicating the evolution of at least two major p17 species (i.e., >20% of the clones) were determined to be more common at positions contained within these CTL epitopes (p < 0.01), The present data suggest that the evolution of the p17 gene is influenced by contact areas with the host HLA class I molecules.