Abstract
Spontaneous resolution of hepatitis C virus (HCV) infection in humans usually affords long-term immunity to persistent viremia and associated liver diseases. Here, we report that memory CD4+ Tcells are essential for this protection. Antibody-mediated depletion of CD4+ Tcells before reinfection of two immune chimpanzees resulted in persistent, low-level viremia despite functional intra-hepatic memory CD8+ Tcell responses. Incomplete control of HCV replication by memory CD8+ Tcells in the absence of adequate CD4+ Tcell help was associated with emergence of viral escape mutations in class I major histocompatibility complex-restricted epitopes and failure to resolve HCV infection.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Amino Acid Substitution
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Animals
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Antigen Presentation
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Antigens, Viral / chemistry
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Antigens, Viral / genetics
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Antigens, Viral / immunology
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CD4-Positive T-Lymphocytes / immunology*
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CD8-Positive T-Lymphocytes / immunology*
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Epitopes
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Evolution, Molecular
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Hepacivirus / genetics
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Hepacivirus / immunology*
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Hepacivirus / physiology*
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Hepatitis C / immunology*
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Hepatitis C / virology
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Immunologic Memory*
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Liver / immunology
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Major Histocompatibility Complex
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Molecular Sequence Data
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Mutation
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Pan troglodytes
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T-Lymphocyte Subsets / immunology
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Time Factors
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Viral Core Proteins / chemistry
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Viral Core Proteins / genetics
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Viral Core Proteins / immunology
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Viral Nonstructural Proteins / chemistry
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Viral Nonstructural Proteins / genetics
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Viral Nonstructural Proteins / immunology
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Viremia
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Virus Replication
Substances
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Antigens, Viral
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Epitopes
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Viral Core Proteins
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Viral Nonstructural Proteins
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nucleocapsid protein, Hepatitis C virus