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A molecular chaperone glucose-regulated protein 94 blocks apoptosis induced by virus infection

Authors
 Song Hee Lee  ;  Ran Song  ;  Mi Nam Lee  ;  Chon Saeng Kim  ;  Hanna Lee  ;  Young-Yun Kong  ;  Hoguen Kim  ;  Sung Key Jang 
Citation
 HEPATOLOGY, Vol.47(3) : 854-866, 2008 
Journal Title
 HEPATOLOGY 
ISSN
 0270-9139 
Issue Date
2008
MeSH
Adult ; Aged ; Apoptosis* ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics ; Cell Line, Tumor ; Female ; Gene Expression ; Hepatitis C/genetics ; Hepatitis C/immunology* ; Humans ; Inhibitor of Apoptosis Proteins ; Liver/metabolism ; Liver/virology ; Male ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism* ; Microtubule-Associated Proteins/genetics ; Middle Aged ; Molecular Chaperones/antagonists & inhibitors ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism* ; NF-kappa B/metabolism ; Neoplasm Proteins/genetics ; RNA, Small Interfering/pharmacology ; Survivin ; TNF Receptor-Associated Factor 2/genetics ; TNF-Related Apoptosis-Inducing Ligand/metabolism ; Tumor Necrosis Factor-alpha/genetics ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism* ; X-Linked Inhibitor of Apoptosis Protein/genetics
Keywords
Adult ; Aged ; Apoptosis* ; CASP8 and FADD-Like Apoptosis Regulating Protein/genetics ; Cell Line, Tumor ; Female ; Gene Expression ; Hepatitis C/genetics ; Hepatitis C/immunology* ; Humans ; Inhibitor of Apoptosis Proteins ; Liver/metabolism ; Liver/virology ; Male ; Membrane Glycoproteins/antagonists & inhibitors ; Membrane Glycoproteins/genetics ; Membrane Glycoproteins/metabolism* ; Microtubule-Associated Proteins/genetics ; Middle Aged ; Molecular Chaperones/antagonists & inhibitors ; Molecular Chaperones/genetics ; Molecular Chaperones/metabolism* ; NF-kappa B/metabolism ; Neoplasm Proteins/genetics ; RNA, Small Interfering/pharmacology ; Survivin ; TNF Receptor-Associated Factor 2/genetics ; TNF-Related Apoptosis-Inducing Ligand/metabolism ; Tumor Necrosis Factor-alpha/genetics ; Viral Envelope Proteins/genetics ; Viral Envelope Proteins/metabolism* ; X-Linked Inhibitor of Apoptosis Protein/genetics
Abstract
The hepatitis C virus (HCV) E2 protein has been shown to block apoptosis and has been suggested to facilitate persistent infection of the virus. Here, we report that the anti-apoptotic activity of E2 is mediated by activation of nuclear factor kappa B (NF-kappaB) that directs expression of survival gene products such as tumor necrosis factor (TNF-alpha) receptor-associated factor 2 (TRAF2), X-chromosome-linked inhibitor of apoptosis protein (XIAP), FLICE-like inhibitory protein (FLIP), and survivin. Increased levels of these proteins were observed in HCV-infected cells and a cell line producing HCV E2 protein. The activation of NF-kappaB was mediated by HCV-E2-induced expression of the molecular chaperone glucose-regulated protein 94 (GRP94). Overexpression of GRP94 alone resulted in expression of anti-apoptotic proteins and blocked apoptosis induced by tumor-necrosis-related apoptosis-inducing ligand (TRAIL). Interestingly, increased levels of GRP94 were observed in cells supporting HCV proliferation that originated from liver tissues from HCV patients. Moreover, small interfering RNA (siRNA) knock-down of GRP94 nullified the anti-apoptotic activity of HCV E2. CONCLUSION: These data indicate that HCV E2 blocks apoptosis induced by HCV infection and the host immune system through overproduction of GRP94, and that HCV E2 plays an important role in persistent HCV infection.
Full Text
http://onlinelibrary.wiley.com/doi/10.1002/hep.22107/abstract
DOI
10.1002/hep.22107
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Pathology (병리학교실) > 1. Journal Papers
Yonsei Authors
Kim, Hogeun(김호근)
Lee, Hanna(이한나)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/107560
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