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Gastroenterology. 2011 Feb;140(2):686-696.e1. doi: 10.1053/j.gastro.2010.09.042. Epub 2010 Sep 24.

Spontaneous control of HCV is associated with expression of HLA-B 57 and preservation of targeted epitopes.

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  • 1Division of Infectious Diseases, Massachusetts General Hospital, Harvard Medical School, GRB-504, Boston, Massachusetts 02114, USA. akim1@partners.org

Abstract

BACKGROUND & AIMS:

HLA class I alleles are linked to spontaneous control of hepatitis C virus (HCV) and human immunodeficiency virus-1, but for HCV the roles of particular alleles and corresponding CD8(+) T-cell responses remain incompletely defined. We aimed to determine the correlations between these alleles and natural outcomes of HCV and determine associated key T-cell responses.

METHODS:

In a cohort of HCV individuals, we determined HLA class I alleles, HCV outcomes, T-cell responses, and examined sequence data for mutational changes within key epitopes.

RESULTS:

Carriage of HLA-B 57 was associated with a higher rate of viral clearance (risk ratio = 2.0; 95% confidence interval: 1.2-3.4), while HLA-B 08 was associated with a lower rate (risk ratio = 0.34; 95% confidence interval: 0.1-0.9]. Two HLA-B 57-restricted T-cell epitopes were targeted in spontaneous clearance; subjects with chronic viremia expressing HLA-B 57 harbored HCV strains with a high frequency of mutations in key residues. HLA-B 57-mediated escape was supported by diminished immune recognition of these variants and acute HCV infection revealing viral evolution toward less recognized variants. Analysis of a genotype 1b strain from a single-source HCV outbreak in which HLA-B 57 was not protective revealed sequence variations that interfere with immunogenicity, thereby preventing HLA-B 57-mediated immune pressure.

CONCLUSIONS:

Our data indicate a role of HLA-B 57-restricted CD8(+) T-cell responses in mediating spontaneous clearance and evolution in HCV infection, and viral strains containing epitope variants that are less recognized abrogate the protective effects of HLA-B 57. The finding that HLA-B 57-mediated antiviral immunity is associated with control of both human immunodeficiency virus-1 and HCV suggests a common shared mechanism of a successful immune response against persistent viruses.

Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

PMID:
20875418
[PubMed - indexed for MEDLINE]
PMCID:
PMC3021586
Free PMC Article

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