title: Knockdown of autophagy enhances the innate immune response in hepatitis C virus-infected hepatocytes.
abstract: The role of autophagy in disease pathogenesis following viral infection is beginning to be elucidated. We have previously reported that hepatitis C virus (HCV) infection in hepatocytes induces autophagy. However, the biological significance of HCV-induced autophagy has not been clarified. Autophagy has recently been identified as a novel component of the innate immune system against viral infection. In this study, we found that knockdown of autophagy-related protein beclin 1 (BCN1) or autophagy-related protein 7 (ATG7) in immortalized human hepatocytes (IHHs) inhibited HCV growth. BCN1- or ATG7-knockdown IHHs, when they were infected with HCV, exhibited increased expression of interferon-β, 2',5'-oligoadenylate synthetase 1, interferon-α, and interferon-α-inducible protein 27 messenger RNAs of the interferon signaling pathways in comparison with infected control IHHs. A subsequent study demonstrated that HCV infection in autophagy-impaired IHHs displayed caspase activation, poly(adenosine diphosphate ribose) polymerase cleavage, and apoptotic cell death.
  
  
  CONCLUSIONS
  The disruption of autophagy machinery in HCV-infected hepatocytes activates the interferon signaling pathway and induces apoptosis. Together, these results suggest that HCV-induced autophagy impairs the innate immune response.
authors.affiliation: Department of Pathology, Saint Louis University, St. Louis, MO 63104, USA.
authors.forename: Shubham
authors.initials: S
authors.lastname: Shrivastava
authors.forename: Amit
authors.initials: A
authors.lastname: Raychoudhuri
authors.forename: Robert
authors.initials: R
authors.lastname: Steele
authors.forename: Ranjit
authors.initials: R
authors.lastname: Ray
authors.forename: Ratna B
authors.initials: RB
authors.lastname: Ray
mesh_terms: D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000235:genetics*; D001343:Autophagy / Q000235:genetics* / Q000502:physiology; D000071193:Autophagy-Related Protein 7; D000071186:Beclin-1; D020169:Caspases / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000254:growth & development / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D022781:Hepatocytes / Q000378:metabolism / Q000473:pathology / Q000821:virology*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D007372:Interferons / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000502:physiology; D044764:Ubiquitin-Activating Enzymes / Q000235:genetics*
chemical_list: D051017:Apoptosis Regulatory Proteins; C491997:BECN1 protein, human; D000071186:Beclin-1; D008565:Membrane Proteins; D034741:RNA, Small Interfering; D007372:Interferons; D020169:Caspases; C509349:ATG7 protein, human; D000071193:Autophagy-Related Protein 7; D044764:Ubiquitin-Activating Enzymes