Viral and immunological determinants of hepatitis C virus clearance, persistence, and disease.
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.
Thimme
Robert
R
Department of Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037, USA.
Bukh
Jens
J
Spangenberg
Hans Christian
HC
Wieland
Stefan
S
Pemberton
Janell
J
Steiger
Carola
C
Govindarajan
Sugantha
S
Purcell
Robert H
RH
Chisari
Francis V
FV
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
D012333:RNA, Messenger; D011993:Recombinant Fusion Proteins; D007372:Interferons