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Hepatitis C virus infection induces the expression of amphiregulin, a factor related to the activation of cellular survival pathways and required for efficient viral assembly.
MedLine Citation:
PMID:  21653755     Owner:  NLM     Status:  Publisher    
Amphiregulin (AREG) is a ligand of epidermal growth factor (EGF) receptor and may play a role in development of cirrhosis and hepatocellular carcinoma in patients infected with hepatitis C virus (HCV). AREG showed an enhanced expression in HCV-infected human hepatoma cells according to gene array analysis. Therefore, we addressed the question about the role of AREG in HCV infection. AREG expression level was elevated in hepatoma cells containing a subgenomic HCV replicon or infected by HCV. Using a reporter assay, AREG promoter activity was found to be upregulated upon HCV infection. The enhanced AREG expression in hepatoma cells was partly caused by dsRNAs, HCV NS3 protein, and autocrine stimulation. AREG was able to activate cellular signaling pathways including ERK, Akt and p38, promote cell proliferation, and protect cells from HCV-induced cell death. Further, knockdown AREG expression increased the efficiency of HCV entry, as proven by HCVpp reporter assay. However, the formation and release of infectious HCV particles were reduced by AREG silencing with a concomitant accumulation of intracellular HCV RNA pool, indicating that the assembly and release of HCV progeny may require AREG expression. Blocking MAPK-ERK pathway by U0126 in Huh7.5.1 cells had the similar effect on HCV replication. In conclusion, HCV infection leads to an increase AREG expression in hepatocytes. AREG expression is essential for the efficient HCV assembly and virion release. Due to the activation of the cellular survival pathways, AREG may counteract HCV-induced apoptosis of infected hepatocytes and facilitate the development of liver cirrhosis and hepatocellular carcinoma.
Rongjuan Pei; Honghe Chen; Lu Lu; Wandi Zhu; Susanne Beckebaum; Vito Cicinnati; Mengji Lu; Xinwen Chen
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-6-8
Journal Detail:
Title:  The Journal of general virology     Volume:  -     ISSN:  1465-2099     ISO Abbreviation:  -     Publication Date:  2011 Jun 
Date Detail:
Created Date:  2011-6-9     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0077340     Medline TA:  J Gen Virol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Wuhan Institute of Virology, Chinese Academy of Sciences;
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