PMID- 23015700
OWN - NLM
STAT- MEDLINE
DCOM- 20130114
LR  - 20211021
IS  - 1098-5514 (Electronic)
IS  - 0022-538X (Print)
IS  - 0022-538X (Linking)
VI  - 86
IP  - 23
DP  - 2012 Dec
TI  - Cytosolic phospholipase A2 gamma is involved in hepatitis C virus replication and 
      assembly.
PG  - 13025-37
LID - 10.1128/JVI.01785-12 [doi]
AB  - Similar to other positive-sense, single-stranded RNA viruses, hepatitis C virus 
      (HCV) replicates its genome in a remodeled intracellular membranous structure 
      known as the membranous web (MW). To date, the process of MW formation remains 
      unclear. It is generally acknowledged that HCV nonstructural protein 4B (NS4B) 
      can induce MW formation through interaction with the cytosolic endoplasmic 
      reticulum (ER) membrane. Many host proteins, such as phosphatidylinositol 
      4-kinase IIIalpha (PI4KIIIalpha), have been identified as critical factors required for 
      this process. We now report a new factor, the cytosolic phospholipase A2 gamma 
      (PLA2G4C), which contributes to MW formation, HCV replication, and assembly. The 
      PLA2G4C gene was identified as a host gene with upregulated expression upon HCV 
      infection. Knockdown of PLA2G4C in HCV-infected cells or HCV replicon-containing 
      cells by small interfering RNA (siRNA) significantly suppressed HCV replication 
      and assembly. In addition, the chemical inhibitor methyl arachidonyl 
      fluorophosphonate (MAFP), which specifically inhibits PLA2, reduced HCV 
      replication and assembly. Electron microscopy demonstrated that MW structure 
      formation was defective after PLA2G4C knockdown in HCV replicon-containing cells. 
      Further analysis by immunostaining and immunoprecipitation assays indicated that 
      PLA2G4C colocalized with the HCV proteins NS4B and NS5A in cells infected with 
      JFH-1 and interacted with NS4B. In addition, PLA2G4C was able to transport the 
      HCV nonstructural proteins from replication sites to lipid droplets, the site for 
      HCV assembly. These data suggest that PLA2G4C plays an important role in the HCV 
      life cycle and might represent a potential target for anti-HCV therapy.
FAU - Xu, Song
AU  - Xu S
AD  - State Key Laboratory of Virology, Wuhan Institute of Virology, Chinese Academy of 
      Sciences, Wuhan, People's Republic of China.
FAU - Pei, Rongjuan
AU  - Pei R
FAU - Guo, Min
AU  - Guo M
FAU - Han, Qingxia
AU  - Han Q
FAU - Lai, Juan
AU  - Lai J
FAU - Wang, Yun
AU  - Wang Y
FAU - Wu, Chunchen
AU  - Wu C
FAU - Zhou, Yuan
AU  - Zhou Y
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 - 20120926
PL  - United States
TA  - J Virol
JT  - Journal of virology
JID - 0113724
RN  - 0 (Arachidonic Acids)
RN  - 0 (DNA Primers)
RN  - 0 (NS4B protein, flavivirus)
RN  - 0 (Organophosphonates)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Viral Nonstructural Proteins)
RN  - 0 (methyl arachidonylfluorophosphonate)
RN  - 27YG812J1I (Arachidonic Acid)
RN  - EC 3.1.1.4 (Group IV Phospholipases A2)
SB  - IM
MH  - Arachidonic Acid/pharmacology
MH  - Arachidonic Acids/pharmacology
MH  - Blotting, Western
MH  - Cell Line
MH  - Cytosol/*metabolism
MH  - DNA Primers/genetics
MH  - Endoplasmic Reticulum/metabolism
MH  - Gene Knockdown Techniques
MH  - Group IV Phospholipases A2/antagonists & inhibitors/*metabolism
MH  - Hepacivirus/*physiology
MH  - Humans
MH  - Immunoprecipitation
MH  - Microscopy, Fluorescence
MH  - Organophosphonates/pharmacology
MH  - Plasmids/genetics
MH  - RNA, Small Interfering/genetics
MH  - Real-Time Polymerase Chain Reaction
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Viral Nonstructural Proteins/metabolism
MH  - Virus Assembly/drug effects/*physiology
MH  - Virus Replication/drug effects/*physiology
PMC - PMC3497680
EDAT- 2012/09/28 06:00
MHDA- 2013/01/15 06:00
PMCR- 2013/06/01
CRDT- 2012/09/28 06:00
PHST- 2012/09/28 06:00 [entrez]
PHST- 2012/09/28 06:00 [pubmed]
PHST- 2013/01/15 06:00 [medline]
PHST- 2013/06/01 00:00 [pmc-release]
AID - JVI.01785-12 [pii]
AID - 01785-12 [pii]
AID - 10.1128/JVI.01785-12 [doi]
PST - ppublish
SO  - J Virol. 2012 Dec;86(23):13025-37. doi: 10.1128/JVI.01785-12. Epub 2012 Sep 26.