Epitopes described in "Cellular immune selection with hepatitis C virus persistence in humans."

Article Authors:Andrea L Cox; Timothy Mosbruger; Qing Mao; Zhi Liu; Xiao-Hong Wang; Hung-Chih Yang; John Sidney; Alessandro Sette; Drew Pardoll; David L Thomas; Stuart C Ray
Article Title:Cellular immune selection with hepatitis C virus persistence in humans.
Reference Detail
Reference ID:1001708
Abstract:Hepatitis C virus (HCV) infection frequently persists despite substantial virus-specific cellular immune responses. To determine if immunologically driven sequence variation occurs with HCV persistence, we coordinately analyzed sequence evolution and CD8+ T cell responses to epitopes covering the entire HCV polyprotein in subjects who were followed prospectively from before infection to beyond the first year. There were no substitutions in T cell epitopes for a year after infection in a subject who cleared viremia. In contrast, in subjects with persistent viremia and detectable T cell responses, we observed substitutions in 69% of T cell epitopes, and every subject had a substitution in at least one epitope. In addition, amino acid substitutions occurred 13-fold more often within than outside T cell epitopes (P < 0.001, range 5-38). T lymphocyte recognition of 8 of 10 mutant peptides was markedly reduced compared with the initial sequence, indicating viral escape. Of 16 nonenvelope substitutions that occurred outside of known T cell epitopes, 8 represented conversion to consensus (P = 0.015). These findings reveal two distinct mechanisms of sequence evolution involved in HCV persistence: viral escape from CD8+ T cell responses and optimization of replicative capacity.
Affiliations:Department of Medicine, Johns Hopkins Medical Institutions, Baltimore, MD 21231, USA. acox@jhmi.edu
Reference Type:Literature
PubMed ID:15939790
Journal:J Exp Med
Journal Volume:201
Article Pages:1741-52
Journal ISSN:1540-9538
Article Chemical List:Epitopes, T-Lymphocyte;Peptides;Viral Structural Proteins
Article MeSH List:Amino Acid Substitution(genetics; immunology); CD8-Positive T-Lymphocytes(immunology); Consensus Sequence(genetics; immunology); Epitopes, T-Lymphocyte(genetics; immunology); Hepacivirus(genetics; immunology); Hepatitis C(genetics; immunology; pathology); Humans; Peptides(genetics; immunology); Polymorphism, Genetic(genetics; immunology); Selection, Genetic; T-Lymphocyte Subsets(immunology); Viral Structural Proteins(genetics; immunology); Viremia(genetics; immunology; pathology); Virus Replication(genetics; immunology)
Curation Last Updated:2011-10-24 21:10:59