Immune evasion versus recovery after acute hepatitis C virus infection from a shared source

Author:

Tester Ian12,Smyk-Pearson Susan12,Wang Ping3,Wertheimer Anne2,Yao Ermei3,Lewinsohn David M.12,Tavis John E.34,Rosen Hugo R.12

Affiliation:

1. Department of Medicine, Portland Veterans Administration Medical Center

2. Department of Molecular Microbiology and Immunology, Oregon Health and Science University, Portland OR 97239

3. Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine

4. Saint Louis University Liver Center, St. Louis, MO 63103

Abstract

Acute infection with hepatitis C virus (HCV) rarely is identified, and hence, the determinants of spontaneous resolution versus chronicity remain incompletely understood. In particular, because of the retrospective nature and unknown source of infection in most human studies, direct evidence for emergence of escape mutations in immunodominant major histocompatibility complex class I–restricted epitopes leading to immune evasion is extremely limited. In two patients infected accidentally with an identical HCV strain but who developed divergent outcomes, the total lack of HCV-specific CD4+ T cells in conjunction with vigorous CD8+ T cells that targeted a single epitope in one patient was associated with mutational escape and viral persistence. Statistical evidence for positive Darwinian selective pressure against an immunodominant epitope is presented. Wild-type cytotoxic T lymphocytes persisted even after the cognate antigen was no longer present.

Publisher

Rockefeller University Press

Subject

Immunology,Immunology and Allergy

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