MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
AbstractHepatitis C virus (HCV) has infected around 160 million individuals. Current therapies have limited efficacy and are fraught with side effects. To identify cellular HCV dependency factors, possible therapeutic targets, we manipulated signaling cascades with pathway-specific inhibitors. Using this approach we identified the MAPK/ERK regulated, cytosolic, calcium-dependent, group IVA phospholipase A2 (PLA2G4A) as a novel HCV dependency factor. Inhibition of PLA2G4A activity reduced core protein abundance at lipid droplets, core envelopment and secretion of particles. Moreover, released particles displayed aberrant protein composition and were 100-fold less infectious. Exogenous addition of arachidonic acid, the cleavage product of PLA2G4A-catalyzed lipolysis, but not other related poly-unsaturated fatty acids restored infectivity. Strikingly, production of infectious Dengue virus, a relative of HCV, was also dependent on PLA2G4A. These results highlight previously unrecognized parallels in the assembly pathways of these human pathogens, and define PLA2G4A-dependent lipolysis as crucial prerequisite for production of highly infectious viral progeny.
CitationMAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles. 2012, 8 (7):e1002829 PLoS Pathog.
AffiliationDivision of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Centre for Infection Research (HZI), Hannover, Germany.
The following license files are associated with this item:
- Cytosolic phospholipase A2 gamma is involved in hepatitis C virus replication and assembly.
- Authors: Xu S, Pei R, Guo M, Han Q, Lai J, Wang Y, Wu C, Zhou Y, Lu M, Chen X
- Issue date: 2012 Dec
- Involvement of ERK pathway in interferon alpha-mediated antiviral activity against hepatitis C virus.
- Authors: Zhao LJ, Wang W, Wang WB, Ren H, Qi ZT
- Issue date: 2015 Mar
- Oxidative stress induces anti-hepatitis C virus status via the activation of extracellular signal-regulated kinase.
- Authors: Yano M, Ikeda M, Abe K, Kawai Y, Kuroki M, Mori K, Dansako H, Ariumi Y, Ohkoshi S, Aoyagi Y, Kato N
- Issue date: 2009 Sep
- Phospholipase A2 regulation of bovine endometrial (BEND) cell prostaglandin production.
- Authors: Godkin JD, Roberts MP, Elgayyar M, Guan W, Tithof PK
- Issue date: 2008 Sep 23
- Hepatitis C virus core protein induces cell proliferation and activates ERK, JNK, and p38 MAP kinases together with the MAP kinase phosphatase MKP-1 in a HepG2 Tet-Off cell line.
- Authors: Erhardt A, Hassan M, Heintges T, Häussinger D
- Issue date: 2002 Jan 20