title: Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease.
abstract: To define the early events that determine the outcome of acute hepatitis C virus (HCV) infection, we compared the course of viremia with the peripheral and intrahepatic T cell response and intrahepatic cytokine profile in six acutely infected chimpanzees. Three different outcomes were observed after peak viral titers were reached: sustained viral clearance, transient viral clearance followed by chronic infection, and chronic infection that persisted at initial peak titers. The results indicate that HCV spread outpaces the T cell response and that HCV rapidly induces but is not controlled by IFN-alphabeta; that viral clearance follows the entry and accumulation of HCV-specific IFN-gamma-producing T cells in the liver; and that it may not require the destruction of infected cells.
authors.affiliation: Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Thimme
authors.forename: Jens
authors.initials: J
authors.lastname: Bukh
authors.forename: Hans Christian
authors.initials: HC
authors.lastname: Spangenberg
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieland
authors.forename: Janell
authors.initials: J
authors.lastname: Pemberton
authors.forename: Carola
authors.initials: C
authors.lastname: Steiger
authors.forename: Sugantha
authors.initials: S
authors.lastname: Govindarajan
authors.forename: Robert H
authors.initials: RH
authors.lastname: Purcell
authors.forename: Francis V
authors.initials: FV
authors.lastname: Chisari
mesh_terms: D000208:Acute Disease; D000818:Animals; D001706:Biopsy; D005786:Gene Expression Regulation; D016174:Hepacivirus / Q000276:immunology / Q000502:physiology*; D006526:Hepatitis C / Q000276:immunology / Q000821:virology*; D007372:Interferons / Q000096:biosynthesis / Q000502:physiology; D008099:Liver / Q000378:metabolism / Q000473:pathology / Q000821:virology; D002679:Pan troglodytes; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D014766:Viremia / Q000276:immunology
chemical_list: D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D007372:Interferons