PMID- 21653755
OWN - NLM
STAT- MEDLINE
DCOM- 20111107
LR  - 20200228
IS  - 1465-2099 (Electronic)
IS  - 0022-1317 (Linking)
VI  - 92
IP  - Pt 10
DP  - 2011 Oct
TI  - 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.
PG  - 2237-2248
LID - 10.1099/vir.0.032581-0 [doi]
AB  - Amphiregulin (AREG) is a ligand of the epidermal growth factor (EGF) receptor and 
      may play a role in the 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 signalling pathways including 
      ERK, Akt and p38, promote cell proliferation, and protect cells from HCV-induced 
      cell death. Further, knockdown of AREG expression increased the efficiency of HCV 
      entry, as proven by HCV pseudoparticles 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 the 
      MAPK-ERK pathway by U0126 in Huh7.5.1 cells had a similar effect on HCV 
      replication. In conclusion, HCV infection leads to an increase in AREG expression 
      in hepatocytes. AREG expression is essential for 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.
FAU - Pei, Rongjuan
AU  - Pei R
AD  - Graduate University of Chinese Academy of Sciences, Beijing, PR China.
AD  - Institute of Virology, University Hospital of Essen, Essen, Germany.
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
FAU - Chen, Honghe
AU  - Chen H
AD  - Graduate University of Chinese Academy of Sciences, Beijing, PR China.
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
FAU - Lu, Lu
AU  - Lu L
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
FAU - Zhu, Wandi
AU  - Zhu W
AD  - Graduate University of Chinese Academy of Sciences, Beijing, PR China.
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
FAU - Beckebaum, Susanne
AU  - Beckebaum S
AD  - Department of Gastroenterology and Hepatology, University Hospital of Essen, 
      Essen, Germany.
FAU - Cicinnati, Vito
AU  - Cicinnati V
AD  - Department of Gastroenterology and Hepatology, University Hospital of Essen, 
      Essen, Germany.
FAU - Lu, Mengji
AU  - Lu M
AD  - Institute of Virology, University Hospital of Essen, Essen, Germany.
FAU - Chen, Xinwen
AU  - Chen X
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, PR China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20110608
PL  - England
TA  - J Gen Virol
JT  - The Journal of general virology
JID - 0077340
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (Glycoproteins)
RN  - 0 (Intercellular Signaling Peptides and Proteins)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Amphiregulin
MH  - Cell Line
MH  - Cell Proliferation
MH  - Cell Survival
MH  - EGF Family of Proteins
MH  - Female
MH  - Gene Expression
MH  - Gene Expression Profiling
MH  - Glycoproteins/*biosynthesis
MH  - Hepacivirus/*pathogenicity
MH  - Hepatitis C/*pathology/*virology
MH  - Hepatocytes/virology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Intercellular Signaling Peptides and Proteins/*biosynthesis
MH  - Male
MH  - Middle Aged
MH  - *Virus Assembly
MH  - *Virus Release
MH  - Young Adult
EDAT- 2011/06/10 06:00
MHDA- 2011/11/08 06:00
CRDT- 2011/06/10 06:00
PHST- 2011/06/10 06:00 [entrez]
PHST- 2011/06/10 06:00 [pubmed]
PHST- 2011/11/08 06:00 [medline]
AID - 10.1099/vir.0.032581-0 [doi]
PST - ppublish
SO  - J Gen Virol. 2011 Oct;92(Pt 10):2237-2248. doi: 10.1099/vir.0.032581-0. Epub 2011 
      Jun 8.