title: Innate host response in primary human hepatocytes with hepatitis C virus infection.
abstract: OBJECTIVE
  The interaction between hepatitis C virus (HCV) and innate antiviral defense systems in primary human hepatocytes is not well understood. The objective of this study is to examine how primary human hepatocytes response to HCV infection.
  
  
  METHODS
  An infectious HCV isolate JFH1 was used to infect isolated primary human hepatocytes. HCV RNA or NS5A protein in the cells was detected by real-time PCR or immunofluorescence staining respectively. Apoptosis was examined with flow cytometry. Mechanisms of HCV-induced IFN-β expression and apoptosis were determined.
  
  
  RESULTS
  Primary human hepatocytes were susceptible to JFH1 virus and released infectious virus. IFN-α inhibited viral RNA replication in the cells. IFN-β and interferon-stimulated genes were induced in the cells during acute infection. HCV infection induced apoptosis of primary human hepatocytes through the TRAIL-mediated pathway. Silencing RIG-I expression in primary human hepatocytes inhibited IFN-β and TRAIL expression and blocked apoptosis of the cells, which facilitated viral RNA replication in the cells. Moreover, HCV NS34A protein inhibited viral induced IFN-β expression in primary human hepatocytes.
  
  
  CONCLUSIONS
  Innate host response is intact in HCV-infected primary human hepatocytes. RIG-I plays a key role in the induction of IFN and TRAIL by viruses and apoptosis of primary human hepatocytes via activation of the TRAIL-mediated pathway. HCV NS34A protein appears to be capable of disrupting the innate antiviral host responses in primary human hepatocytes. Our study provides a novel mechanism by which primary human hepatocytes respond to natural HCV infection.
authors.affiliation: Department of Molecular Medicine, College of Biology of Hunan University, Changsha, China.
authors.forename: Darong
authors.initials: D
authors.lastname: Yang
authors.forename: Nianli
authors.initials: N
authors.lastname: Liu
authors.forename: Chaohui
authors.initials: C
authors.lastname: Zuo
authors.forename: Shoahua
authors.initials: S
authors.lastname: Lei
authors.forename: Xinjiao
authors.initials: X
authors.lastname: Wu
authors.forename: Fei
authors.initials: F
authors.lastname: Zhou
authors.forename: Chen
authors.initials: C
authors.lastname: Liu
authors.forename: Haizhen
authors.initials: H
authors.lastname: Zhu
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases / Q000235:genetics; D016174:Hepacivirus / Q000276:immunology; D006526:Hepatitis C / Q000276:immunology*; D022781:Hepatocytes / Q000276:immunology / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000235:genetics; D012367:RNA, Viral / Q000032:analysis; D011971:Receptors, Immunologic; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000235:genetics; D015533:Transcriptional Activation; D014764:Viral Proteins / Q000502:physiology
chemical_list: D012367:RNA, Viral; D011971:Receptors, Immunologic; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014764:Viral Proteins; D016899:Interferon-beta; C452820:RIGI protein, human; D000071457:DEAD Box Protein 58; D053487:DEAD-box RNA Helicases
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