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

Authors
Journal
Journal of Experimental Medicine
0022-1007
Publisher
The Rockefeller University Press
Publication Date
Volume
201
Issue
11
Identifiers
DOI: 10.1084/jem.20042284
Keywords
  • Brief Definitive Report
Disciplines
  • Medicine

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.

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