PMID- 23001481
OWN - NLM
STAT- MEDLINE
DCOM- 20130304
LR  - 20211021
IS  - 1995-820X (Electronic)
IS  - 1674-0769 (Print)
IS  - 1995-820X (Linking)
VI  - 27
IP  - 5
DP  - 2012 Oct
TI  - Regulation of hepatitis C virus replication and gene expression by the MAPK-ERK 
      pathway.
PG  - 278-85
LID - 10.1007/s12250-012-3257-6 [doi]
AB  - The mitogen activated protein kinases-extracellular signal regulated kinases 
      (MAPK-ERK) pathway is involved in regulation of multiple cellular processes 
      including the cell cycle. In the present study using a Huh7 cell line Con1 with 
      an HCV replicon, we have shown that the MAPK-ERK pathway plays a significant role 
      in the modulation of HCV replication and protein expression and might influence 
      IFN-alpha signalling. Epithelial growth factor (EGF) was able to stimulate ERK 
      activation and decreased HCV RNA load while a MAPK-ERK pathway inhibitor U0126 
      led to an elevated HCV RNA load and higher NS5A protein amounts in Con1 cells. It 
      could be further demonstrated that the inhibition of the MAPK-ERK pathway 
      facilitated the translation directed by the HCV internal ribosome entry site. 
      Consistently, a U0126 treatment enhanced activity of the HCV reporter replicon in 
      transient transfection assays. Thus, the MAPK-ERK pathway plays an important role 
      in the regulation of HCV gene expression and replication. In addition, 
      cyclin-dependent kinases (CDKs) downstream of ERK may also be involved in the 
      modulation of HCV replication since roscovitine, an inhibitor of CDKs had a 
      similar effect to that of U0126. Modulation of the cell cycle progression by cell 
      cycle inhibitor or RNAi resulted consistently in changes of HCV RNA levels. 
      Further, the replication of HCV replicon in Con1 cells was inhibited by IFN-alpha. 
      The inhibitory effect of IFN-alpha could be partly reversed by pre-incubation of 
      Con-1 cells with inhibitors of the MAPK-ERK pathway and CDKs. It could be shown 
      that the MAPK-ERK inhibitors are able to partially modulate the expression of 
      interferon-stimulated genes.
FAU - Pei, Rongjuan
AU  - Pei R
AD  - Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan 430071, China.
FAU - Zhang, Xiaoyong
AU  - Zhang X
FAU - Xu, Song
AU  - Xu S
FAU - Meng, Zhongji
AU  - Meng Z
FAU - Roggendorf, Michael
AU  - Roggendorf M
FAU - Lu, Mengji
AU  - Lu M
FAU - Chen, Xinwen
AU  - Chen X
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120921
PL  - Netherlands
TA  - Virol Sin
JT  - Virologica Sinica
JID - 101514185
RN  - 0 (Interferon-alpha)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Cell Line
MH  - *Gene Expression Regulation, Viral
MH  - Hepacivirus/genetics/*physiology
MH  - Hepatocytes/virology
MH  - Humans
MH  - Interferon-alpha/immunology
MH  - *MAP Kinase Signaling System
MH  - Viral Proteins/biosynthesis
MH  - *Virus Replication
PMC - PMC8218137
EDAT- 2012/09/25 06:00
MHDA- 2013/03/05 06:00
PMCR- 2013/09/21
CRDT- 2012/09/25 06:00
PHST- 2012/04/26 00:00 [received]
PHST- 2012/08/17 00:00 [accepted]
PHST- 2012/09/25 06:00 [entrez]
PHST- 2012/09/25 06:00 [pubmed]
PHST- 2013/03/05 06:00 [medline]
PHST- 2013/09/21 00:00 [pmc-release]
AID - 3257 [pii]
AID - 10.1007/s12250-012-3257-6 [doi]
PST - ppublish
SO  - Virol Sin. 2012 Oct;27(5):278-85. doi: 10.1007/s12250-012-3257-6. Epub 2012 Sep 
      21.