Abstract
Cytotoxic T lymphocytes (CTLs) are critical for the control of human immunodeficiency virus, but containment of virus replication can be undermined by mutations in CTL epitopes that lead to virus escape. We analyzed the evolution in vivo of an immunodominant, HLA-A2-restricted CTL epitope and found two principal, diametrically opposed evolutionary pathways that exclusively affect T cell-receptor contact residues. One pathway was characterized by acquisition of CTL escape mutations and the other by selection for wild-type amino acids. The pattern of CTL responses to epitope variants shaped which variant(s) prevailed in the virus population. The pathways notably influenced the amount of plasma virus, as patients with efficient CTL selection had lower plasma viral loads than did patients without efficient selection. Thus, viral escape from CTL responses does not necessarily correlate with disease progression.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adult
-
Amino Acid Sequence
-
Crystallography, X-Ray
-
Evolution, Molecular
-
Female
-
Gene Products, gag / chemistry
-
Gene Products, gag / genetics
-
Gene Products, gag / immunology
-
Genetic Variation
-
HIV Antigens / genetics*
-
HIV Antigens / metabolism
-
HIV Infections / immunology
-
HIV Infections / virology
-
HIV-1 / genetics*
-
HIV-1 / immunology*
-
HLA-A2 Antigen / chemistry
-
HLA-A2 Antigen / metabolism
-
Humans
-
Immunodominant Epitopes / genetics
-
Immunodominant Epitopes / metabolism
-
Models, Molecular
-
Molecular Sequence Data
-
Multiprotein Complexes
-
Mutation
-
Peptide Fragments / chemistry
-
Peptide Fragments / genetics
-
Peptide Fragments / immunology
-
Phylogeny
-
Receptors, Antigen, T-Cell / metabolism*
-
Selection, Genetic
-
T-Lymphocytes, Cytotoxic / immunology
-
Viremia / immunology
-
Viremia / virology
-
env Gene Products, Human Immunodeficiency Virus
Substances
-
Gene Products, gag
-
HIV Antigens
-
HLA-A2 Antigen
-
Immunodominant Epitopes
-
Multiprotein Complexes
-
Peptide Fragments
-
Receptors, Antigen, T-Cell
-
env Gene Products, Human Immunodeficiency Virus
-
p17 gag peptide, human immunodeficiency virus