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 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). 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.
Birk
M
M
Division of Clinical Virology, Huddinge University Hospital, Sweden.
Vahlne
A
A
Sönnerborg
A
A
Sällberg
M
M
D000328:Adult; D001483:Base Sequence; D003001:Cloning, Molecular; D016384:Consensus Sequence; D018604:Epitope Mapping; D000939:Epitopes; D015683:Gene Products, gag / Q000737:chemistry / Q000235:genetics*; D005805:Genes, MHC Class I; D005814:Genes, Viral / Q000235:genetics; D014644:Genetic Variation; D015488:HIV Antigens / Q000737:chemistry / Q000235:genetics*; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000737:chemistry / Q000235:genetics* / Q000276:immunology*; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017421:Sequence Analysis; D013045:Species Specificity; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus
D000939:Epitopes; D015683:Gene Products, gag; D015488:HIV Antigens; D015395:Histocompatibility Antigens Class I; D014764:Viral Proteins; D054301:gag Gene Products, Human Immunodeficiency Virus; C054858:p17 protein, Human Immunodeficiency Virus Type 1