MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles.

2.50
Hdl Handle:
http://hdl.handle.net/10033/247012
Title:
MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles.
Authors:
Menzel, Nicolas; Fischl, Wolfgang; Hueging, Kathrin; Bankwitz, Dorothea; Frentzen, Anne; Haid, Sibylle; Gentzsch, Juliane; Kaderali, Lars; Bartenschlager, Ralf; Pietschmann, Thomas
Abstract:
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.
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.
Citation:
MAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles. 2012, 8 (7):e1002829 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Jul-2012
URI:
http://hdl.handle.net/10033/247012
DOI:
10.1371/journal.ppat.1002829
PubMed ID:
22911431
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
Publications of the Twincore unit Experimental Virology(EVIR)

Full metadata record

DC FieldValue Language
dc.contributor.authorMenzel, Nicolasen_GB
dc.contributor.authorFischl, Wolfgangen_GB
dc.contributor.authorHueging, Kathrinen_GB
dc.contributor.authorBankwitz, Dorotheaen_GB
dc.contributor.authorFrentzen, Anneen_GB
dc.contributor.authorHaid, Sibylleen_GB
dc.contributor.authorGentzsch, Julianeen_GB
dc.contributor.authorKaderali, Larsen_GB
dc.contributor.authorBartenschlager, Ralfen_GB
dc.contributor.authorPietschmann, Thomasen_GB
dc.date.accessioned2012-10-04T14:40:26Z-
dc.date.available2012-10-04T14:40:26Z-
dc.date.issued2012-07-
dc.identifier.citationMAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles. 2012, 8 (7):e1002829 PLoS Pathog.en_GB
dc.identifier.issn1553-7374-
dc.identifier.pmid22911431-
dc.identifier.doi10.1371/journal.ppat.1002829-
dc.identifier.urihttp://hdl.handle.net/10033/247012-
dc.description.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.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen_GB
dc.titleMAP-Kinase Regulated Cytosolic Phospholipase A2 Activity Is Essential for Production of Infectious Hepatitis C Virus Particles.en
dc.typeArticleen
dc.contributor.departmentDivision 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.en_GB
dc.identifier.journalPLoS pathogensen_GB

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