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      HCV persistence and immune evasion in the absence of memory T cell help.

      Science (New York, N.Y.)

      Amino Acid Sequence, Amino Acid Substitution, Animals, Antigen Presentation, Antigens, Viral, chemistry, genetics, immunology, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Epitopes, Evolution, Molecular, Hepacivirus, physiology, Hepatitis C, virology, Immunologic Memory, Liver, Major Histocompatibility Complex, Molecular Sequence Data, Mutation, Pan troglodytes, T-Lymphocyte Subsets, Time Factors, Viral Core Proteins, Viral Nonstructural Proteins, Viremia, Virus Replication

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          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.

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          Journal
          14576438
          10.1126/science.1088774

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