UNLABELLED: 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. CONCLUSION: 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.
UNLABELLED: 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. CONCLUSION: 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: Gregory L Armstrong; Annemarie Wasley; Edgar P Simard; Geraldine M McQuillan; Wendi L Kuhnert; Miriam J Alter Journal: Ann Intern Med Date: 2006-05-16 Impact factor: 25.391
Authors: Jong Ha Jung; Ji Hoon Park; Min Hyeok Jee; Sun Ju Keum; Min-Sun Cho; Seung Kew Yoon; Sung Key Jang Journal: J Virol Date: 2011-07-13 Impact factor: 5.103
Authors: Partha K Chandra; Lili Bao; Kyoungsub Song; Fatma M Aboulnasr; Darren P Baker; Nathan Shores; William C Wimley; Shuanghu Liu; Curt H Hagedorn; Serge Y Fuchs; Tong Wu; Luis A Balart; Srikanta Dash Journal: Am J Pathol Date: 2013-11-09 Impact factor: 4.307