Cytotoxic T-lymphocyte antigen 4 gene and recovery from hepatitis B virus infection

Chloe L. Thio, Timothy L. Mosbruger, Richard A. Kaslow, Christopher L. Karp, Steffanie A. Strathdee, David Vlahov, Stephen J. O'Brien, Jacquie Astemborski, David L. Thomas

Research output: Contribution to journalArticlepeer-review

Abstract

Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is an inhibitory T-cell receptor expressed by activated and regulatory T cells. We hypothesized that single-nucleotide polymorphisms (SNPs) in the gene encoding CTLA-4 may affect the vigor of the T-cell response to hepatitis B virus (HBV) infection, thus influencing viral persistence. To test this hypothesis, we genotyped six CTLA4 SNPs, from which all frequent haplotypes can be determined, using a large, matched panel of subjects with known HBV outcomes. Haplotypes with these SNPs were constructed for each subject using PHASE software. The haplotype distribution differed between those with viral persistence and those with clearance. Two haplotypes were associated with clearance of HBV infection, which was most likely due to associations with the SNPs -1722C (odds ratio [OR] = 0.60, P = 0.06) and +49G (OR = 0.73, P = 0.02). The wild-type haplotype, which contains an SNP leading to a decreased T-cell response (+6230A), was associated with viral persistence (OR = 1.32, P = 0.04). These data suggest that CTLA4 influences recovery from HBV infection, which is consistent with the emerging role of T regulatory cells in the pathogenesis of disease.

Original languageEnglish (US)
Pages (from-to)11258-11262
Number of pages5
JournalJournal of virology
Volume78
Issue number20
DOIs
StatePublished - Oct 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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