title: The clearance of hepatitis C virus infection in chimpanzees may not necessarily correlate with the appearance of acquired immunity.
abstract: Clearance of hepatitis C virus (HCV) infection in humans and chimpanzees is thought to be associated with the induction of strong T-cell responses. We studied four chimpanzees infected with HCV derived from an infectious full-length HCV genotype 1b cDNA. Two of the chimpanzees cleared the infection to undetectable levels for more than 12 months of follow-up; the other two became persistently infected. Detailed analyses of HCV-specific immune responses were performed during the courses of infection in these chimpanzees. Only weak and transient T helper responses were detected during the acute phase in all four chimpanzees. A comparison of the frequency of gamma interferon (IFN-gamma)-producing CD4(+) and CD8(+) T cells in peripheral blood by ELISpot assay did not reveal any correlation between viral clearance and T-cell responses. In addition, analyses of IFN-gamma, IFN-alpha, and interleukin-4 mRNA levels in liver biopsies, presumably indicative of intrahepatic T-cell responses, revealed no distinct pattern in these chimpanzees with respect to infection outcome. The present study suggests that the outcome of HCV infection in chimpanzees is not necessarily attributable to HCV sequence variation and that chimpanzees may recover from HCV infection by mechanisms other than the induction of readily detectable HCV-specific T-cell responses.
authors.affiliation: Liver Diseases Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Thomson
authors.forename: Michelina
authors.initials: M
authors.lastname: Nascimbeni
authors.forename: Michael B
authors.initials: MB
authors.lastname: Havert
authors.forename: Marian
authors.initials: M
authors.lastname: Major
authors.forename: Sophia
authors.initials: S
authors.lastname: Gonzales
authors.forename: Harvey
authors.initials: H
authors.lastname: Alter
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Feinstone
authors.forename: Krishna K
authors.initials: KK
authors.lastname: Murthy
authors.forename: Barbara
authors.initials: B
authors.lastname: Rehermann
authors.forename: T Jake
authors.initials: TJ
authors.lastname: Liang
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D018076:DNA, Complementary; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology / Q000628:therapy* / Q000821:virology; D016898:Interferon-alpha / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D007371:Interferon-gamma / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D008099:Liver / Q000378:metabolism; D008969:Molecular Sequence Data; D002679:Pan troglodytes; D012367:RNA, Viral / Q000302:isolation & purification
chemical_list: D018076:DNA, Complementary; D016898:Interferon-alpha; D012367:RNA, Viral; D015847:Interleukin-4; D007371:Interferon-gamma