Nonsynonymous Mutations within the Human Immunodeficiency Virus Type 1 pl7 Gene Are Clustered to Sequences Binding to the Host Human Leukocyte Antigen Class I Molecules

Abstract

We have analyzed the relation between intrapatient variabilities of the pl7 gene and the location of known host pl7 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 pl7 CTL epitopes corresponded to the HLA class I restriction elements of each patient. An average of 28 ± 16% of the pl7 gene of each patient encoded CTL epitopes corresponding to the HLA restriction elements of the host. Twenty full-length pl7 gene clones were sequenced from each patient. The intrapatient homology between the pl7 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 pl7 clones was noted. Fifteen (16%) of 96 synonymous substitutions were 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). Sub-sequently, variable residues indicating the evolution of at least two major pl7 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.