MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles.
Name:
Menzel et al_final.pdf
Size:
1.506Mb
Format:
PDF
Description:
Opoen Access publication
Average rating
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.
Star rating
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Authors
Menzel, NicolasFischl, Wolfgang
Hueging, Kathrin
Bankwitz, Dorothea
Frentzen, Anne
Haid, Sibylle
Gentzsch, Juliane
Kaderali, Lars
Bartenschlager, Ralf
Pietschmann, Thomas
Issue Date
2012-07
Metadata
Show full item recordAbstract
Hepatitis 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.Citation
MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles. 2012, 8 (7):e1002829 PLoS Pathog.Affiliation
Division 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.Journal
PLoS pathogensPubMed ID
22911431Type
ArticleLanguage
enISSN
1553-7374ae974a485f413a2113503eed53cd6c53
10.1371/journal.ppat.1002829
Scopus Count
The following license files are associated with this item:
Related articles
- 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
- Nonstructural 3 Protein of Hepatitis C Virus Modulates the Tribbles Homolog 3/Akt Signaling Pathway for Persistent Viral Infection.
- Authors: Tran SC, Pham TM, Nguyen LN, Park EM, Lim YS, Hwang SB
- Issue date: 2016 Aug 15
- Signal transduction pathways for activation of extracellular signal-regulated kinase by arachidonic acid in rat neutrophils.
- Authors: Chang LC, Wang JP
- Issue date: 2001 Apr