HCV persistence and immune evasion in the absence of memory T cell help.
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.
Grakoui
Arash
A
Center for the Study of Hepatitis C, Rockefeller University, New York, NY 10021, USA.
Shoukry
Naglaa H
NH
Woollard
David J
DJ
Han
Jin-Hwan
JH
Hanson
Holly L
HL
Ghrayeb
John
J
Murthy
Krishna K
KK
Rice
Charles M
CM
Walker
Christopher M
CM
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D017951:Antigen Presentation; D000956:Antigens, Viral / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D000939:Epitopes; D019143:Evolution, Molecular; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D007156:Immunologic Memory; D008099:Liver / Q000276:immunology; D008285:Major Histocompatibility Complex; D008969:Molecular Sequence Data; D009154:Mutation; D002679:Pan troglodytes; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013997:Time Factors; D014758:Viral Core Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000737:chemistry / Q000235:genetics / Q000276:immunology; D014766:Viremia; D014779:Virus Replication
D000956:Antigens, Viral; D000939:Epitopes; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; C069130:nucleocapsid protein, Hepatitis C virus