title: The immunologic basis for hepatitis C infection.
abstract: OBJECTIVE
  The host immune system is arguably involved in nearly every step of hepatitis C virus (HCV) infection. In patients, the outcome, whether it is a natural infection or results from an interferon-alpha-based treatment, is determined by a series of complex host-virus interactions. In this review, we focus on the state of research addressing the immune mechanisms critical for viral clearance and disease resolution. Additional discussion is devoted to the evasion and blockade tactics of HCV as well as to current efforts aimed at disrupting the replication cycle of this well-evolved virus. Current theories of immune-mediated injury of hepatocytes are also discussed.
  
  
  RESULTS
  Strong and persistent CD8 and CD4 T-cell responses are critical in HCV clearance. Although each may play a unique role in the process, the intrahepatic interferon (IFN)-gamma produced by these cells is central to their antiviral action. IFN-alpha/beta alone, without triggering subsequent HCV-specific T-cell responses, may not lead to a sustained viral response in vivo. Synergism among several immune cells, including T, NK, and NKT cells is important for disease resolution. Additional data raise the possibility that viral clearance and liver injury are mediated through different effector mechanisms of T cells. HCV employs evasion and sabotage tactics to escape from the host's immune system. HCV NS3/4A serine protease can block viral activation of a key transcription factor in initiating cellular IFN response. A newly identified NS3 protease inhibitor can result in a reduction of viremia, illustrating the potential of the viral-enzyme-targeted drug in patients.
  
  
  CONCLUSIONS
  Current data provide a rationale to further explore immune augmentation as a therapeutic intervention in HCV infection.
authors.affiliation: Department of Microbiology and Immunology, University of Texas Medical Branch at Galveston, Galveston, Texas 77555-1019, USA. jisun@utmb.edu
authors.forename: Jiaren
authors.initials: J
authors.lastname: Sun
authors.forename: Kui
authors.initials: K
authors.lastname: Li
authors.forename: Mohamed Tarek
authors.initials: MT
authors.lastname: Shata
authors.forename: Teh-sheng
authors.initials: TS
authors.lastname: Chan