PMID- 19628242
OWN - NLM
STAT- MEDLINE
DCOM- 20090831
LR  - 20220330
IS  - 1096-0341 (Electronic)
IS  - 0042-6822 (Linking)
VI  - 391
IP  - 2
DP  - 2009 Sep 1
TI  - Hepatitis C virus NS4B induces unfolded protein response and endoplasmic 
      reticulum overload response-dependent NF-kappaB activation.
PG  - 257-64
LID - 10.1016/j.virol.2009.06.039 [doi]
AB  - Hepatitis C virus nonstructural protein 4B (NS4B) is an endoplasmic reticulum 
      (ER) membrane associated protein and a potent causative factor of ER stress. Here 
      we reported that unfolded protein response (UPR) can be activated by HCV NS4B 
      through inducing both XBP1 mRNA splicing and ATF6 cleavage in human hepatic 
      cells. Flow cytometric analysis revealed that HCV NS4B stimulates the production 
      of reactive oxygen species (ROS) by perturbing intracellular Ca(2+) homeostasis. 
      Luciferase assay showed that HCV NS4B also activates the multifunctional 
      transcription factor, NF-kappaB, in a dose-dependent manner through Ca(2+) 
      signaling and ROS. Further immunoblot analysis showed that HCV NS4B promotes 
      NF-kappaB translocation into the nucleus via protein-tyrosine kinase (PTK) 
      mediated phosphorylation and subsequent degradation of IkappaBalpha. These 
      studies provide an important insight into the implication of NS4B in HCV life 
      cycle and HCV-associated liver disease by affecting host intracellular signal 
      transduction pathways.
FAU - Li, Shanshan
AU  - Li S
AD  - State Key Laboratory of Virology, College of Life Sciences, Wuhan University, 
      Wuhan, Hubei 430072, China.
FAU - Ye, Linbai
AU  - Ye L
FAU - Yu, Xilan
AU  - Yu X
FAU - Xu, Bo
AU  - Xu B
FAU - Li, Kuntai
AU  - Li K
FAU - Zhu, Xiangdong
AU  - Zhu X
FAU - Liu, Haoju
AU  - Liu H
FAU - Wu, Xiaoyu
AU  - Wu X
FAU - Kong, Lingbao
AU  - Kong L
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090722
PL  - United States
TA  - Virology
JT  - Virology
JID - 0110674
RN  - 0 (ATF6 protein, human)
RN  - 0 (Activating Transcription Factor 6)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (I-kappa B Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (NFKBIA protein, human)
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Regulatory Factor X Transcription Factors)
RN  - 0 (Transcription Factors)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 0 (X-Box Binding Protein 1)
RN  - 0 (XBP1 protein, human)
RN  - 139874-52-5 (NF-KappaB Inhibitor alpha)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Activating Transcription Factor 6/metabolism
MH  - Calcium/metabolism
MH  - Cell Line
MH  - Cell Nucleus/chemistry
MH  - Cytoplasm/chemistry
MH  - DNA-Binding Proteins/metabolism
MH  - Endoplasmic Reticulum/*metabolism
MH  - Hepacivirus/*physiology
MH  - Hepatocytes/*virology
MH  - Humans
MH  - I-kappa B Proteins/metabolism
MH  - NF-KappaB Inhibitor alpha
MH  - NF-kappa B/*biosynthesis
MH  - Reactive Oxygen Species/metabolism
MH  - Regulatory Factor X Transcription Factors
MH  - Transcription Factors/metabolism
MH  - Viral Nonstructural Proteins/*metabolism
MH  - X-Box Binding Protein 1
EDAT- 2009/07/25 09:00
MHDA- 2009/09/01 06:00
CRDT- 2009/07/25 09:00
PHST- 2009/04/14 00:00 [received]
PHST- 2009/05/25 00:00 [revised]
PHST- 2009/06/22 00:00 [accepted]
PHST- 2009/07/25 09:00 [entrez]
PHST- 2009/07/25 09:00 [pubmed]
PHST- 2009/09/01 06:00 [medline]
AID - S0042-6822(09)00390-0 [pii]
AID - 10.1016/j.virol.2009.06.039 [doi]
PST - ppublish
SO  - Virology. 2009 Sep 1;391(2):257-64. doi: 10.1016/j.virol.2009.06.039. Epub 2009 
      Jul 22.