PMID- 24898729
OWN - NLM
STAT- MEDLINE
DCOM- 20150616
LR  - 20141016
IS  - 1462-5822 (Electronic)
IS  - 1462-5814 (Linking)
VI  - 16
IP  - 11
DP  - 2014 Nov
TI  - Reticulon 3 interacts with NS4B of the hepatitis C virus and negatively regulates 
      viral replication by disrupting NS4B self-interaction.
PG  - 1603-18
LID - 10.1111/cmi.12318 [doi]
AB  - The non-structural protein 4B (NS4B) of the hepatitis C virus (HCV) is an 
      endoplasmic reticulum (ER) membrane protein comprising two consecutive 
      amphipathic alpha-helical domains (AH1 and AH2). Its self-oligomerization via the AH2 
      domain is required for the formation of the membranous web that is necessary for 
      viral replication. Previously, we reported that the host-encoded ER-associated 
      reticulon 3 (RTN3) protein is involved in the formation of the 
      replication-associated membranes of (+)RNA enteroviruses during viral 
      replication. In this study, we demonstrated that the second transmembrane region 
      of RTN3 competed for, and bound to, the AH2 domain of NS4B, thus abolishing NS4B 
      self-interaction and leading to the downregulation of viral replication. This 
      interaction was mediated by two crucial residues, lysine 52 and tyrosine 63, of 
      AH2, and was regulated by the AH1 domain. The silencing of RTN3 in Huh7 and AVA5 
      cells harbouring an HCV replicon enhanced the replication of HCV, which was 
      counteracted by the overexpression of recombinant RTN3. The synthesis of viral 
      RNA was also increased in siRNA-transfected human primary hepatocytes infected 
      with HCV derived from cell culture. Our results demonstrated that RTN3 acted as a 
      restriction factor to limit the replication of HCV.
CI  - (c) 2014 John Wiley & Sons Ltd.
FAU - Wu, Ming-Jhan
AU  - Wu MJ
AD  - Graduate Institute of Biomedical Sciences, Chang Gung University, Taoyuan, 
      Taiwan.
FAU - Ke, Po-Yuan
AU  - Ke PY
FAU - Hsu, John T-A
AU  - Hsu JT
FAU - Yeh, Chau-Ting
AU  - Yeh CT
FAU - Horng, Jim-Tong
AU  - Horng JT
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140707
PL  - India
TA  - Cell Microbiol
JT  - Cellular microbiology
JID - 100883691
RN  - 0 (Carrier Proteins)
RN  - 0 (Membrane Proteins)
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (RTN3 protein, human)
RN  - 0 (Viral Nonstructural Proteins)
SB  - IM
MH  - Carrier Proteins/*metabolism
MH  - Cells, Cultured
MH  - Hepacivirus/*immunology/*physiology
MH  - Hepatocytes/virology
MH  - *Host-Pathogen Interactions
MH  - Humans
MH  - Membrane Proteins/*metabolism
MH  - Nerve Tissue Proteins/*metabolism
MH  - Protein Binding
MH  - Protein Interaction Domains and Motifs
MH  - Protein Interaction Mapping
MH  - *Protein Multimerization
MH  - Viral Nonstructural Proteins/*metabolism
MH  - *Virus Replication
EDAT- 2014/06/06 06:00
MHDA- 2015/06/17 06:00
CRDT- 2014/06/06 06:00
PHST- 2013/12/12 00:00 [received]
PHST- 2014/05/14 00:00 [revised]
PHST- 2014/05/16 00:00 [accepted]
PHST- 2014/06/06 06:00 [entrez]
PHST- 2014/06/06 06:00 [pubmed]
PHST- 2015/06/17 06:00 [medline]
AID - 10.1111/cmi.12318 [doi]
PST - ppublish
SO  - Cell Microbiol. 2014 Nov;16(11):1603-18. doi: 10.1111/cmi.12318. Epub 2014 Jul 7.