2.50
Hdl Handle:
http://hdl.handle.net/10033/246951
Title:
Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade.
Authors:
Fliss, Patricia M; Jowers, Tali Pechenick; Brinkmann, Melanie M; Holstermann, Barbara; Mack, Claudia; Dickinson, Paul; Hohenberg, Heinrich; Ghazal, Peter; Brune, Wolfram
Abstract:
The early host response to viral infections involves transient activation of pattern recognition receptors leading to an induction of inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Subsequent activation of cytokine receptors in an autocrine and paracrine manner results in an inflammatory cascade. The precise mechanisms by which viruses avert an inflammatory cascade are incompletely understood. Nuclear factor (NF)-κB is a central regulator of the inflammatory signaling cascade that is controlled by inhibitor of NF-κB (IκB) proteins and the IκB kinase (IKK) complex. In this study we show that murine cytomegalovirus inhibits the inflammatory cascade by blocking Toll-like receptor (TLR) and IL-1 receptor-dependent NF-κB activation. Inhibition occurs through an interaction of the viral M45 protein with the NF-κB essential modulator (NEMO), the regulatory subunit of the IKK complex. M45 induces proteasome-independent degradation of NEMO by targeting NEMO to autophagosomes for subsequent degradation in lysosomes. We propose that the selective and irreversible degradation of a central regulatory protein by autophagy represents a new viral strategy to dampen the inflammatory response.
Affiliation:
Heinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.
Citation:
Viral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade. 2012, 8 (2):e1002517 PLoS Pathog.
Journal:
PLoS pathogens
Issue Date:
Feb-2012
URI:
http://hdl.handle.net/10033/246951
DOI:
10.1371/journal.ppat.1002517
PubMed ID:
22319449
Type:
Article
Language:
en
ISSN:
1553-7374
Appears in Collections:
publications of the NG Virale Immunmodulation (VIMM)

Full metadata record

DC FieldValue Language
dc.contributor.authorFliss, Patricia Men_GB
dc.contributor.authorJowers, Tali Pechenicken_GB
dc.contributor.authorBrinkmann, Melanie Men_GB
dc.contributor.authorHolstermann, Barbaraen_GB
dc.contributor.authorMack, Claudiaen_GB
dc.contributor.authorDickinson, Paulen_GB
dc.contributor.authorHohenberg, Heinrichen_GB
dc.contributor.authorGhazal, Peteren_GB
dc.contributor.authorBrune, Wolframen_GB
dc.date.accessioned2012-10-04T09:19:33Z-
dc.date.available2012-10-04T09:19:33Z-
dc.date.issued2012-02-
dc.identifier.citationViral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade. 2012, 8 (2):e1002517 PLoS Pathog.en_GB
dc.identifier.issn1553-7374-
dc.identifier.pmid22319449-
dc.identifier.doi10.1371/journal.ppat.1002517-
dc.identifier.urihttp://hdl.handle.net/10033/246951-
dc.description.abstractThe early host response to viral infections involves transient activation of pattern recognition receptors leading to an induction of inflammatory cytokines such as interleukin-1β (IL-1β) and tumor necrosis factor α (TNFα). Subsequent activation of cytokine receptors in an autocrine and paracrine manner results in an inflammatory cascade. The precise mechanisms by which viruses avert an inflammatory cascade are incompletely understood. Nuclear factor (NF)-κB is a central regulator of the inflammatory signaling cascade that is controlled by inhibitor of NF-κB (IκB) proteins and the IκB kinase (IKK) complex. In this study we show that murine cytomegalovirus inhibits the inflammatory cascade by blocking Toll-like receptor (TLR) and IL-1 receptor-dependent NF-κB activation. Inhibition occurs through an interaction of the viral M45 protein with the NF-κB essential modulator (NEMO), the regulatory subunit of the IKK complex. M45 induces proteasome-independent degradation of NEMO by targeting NEMO to autophagosomes for subsequent degradation in lysosomes. We propose that the selective and irreversible degradation of a central regulatory protein by autophagy represents a new viral strategy to dampen the inflammatory response.en_GB
dc.language.isoenen
dc.rightsArchived with thanks to PLoS pathogensen_GB
dc.subject.meshAnimalsen_GB
dc.subject.meshAutophagyen_GB
dc.subject.meshI-kappa B Kinaseen_GB
dc.subject.meshInflammationen_GB
dc.subject.meshInterleukin-1betaen_GB
dc.subject.meshIntracellular Signaling Peptides and Proteinsen_GB
dc.subject.meshMiceen_GB
dc.subject.meshMuromegalovirusen_GB
dc.subject.meshNF-kappa Ben_GB
dc.subject.meshNIH 3T3 Cellsen_GB
dc.subject.meshPhagosomesen_GB
dc.subject.meshReceptors, Interleukin-1en_GB
dc.subject.meshSignal Transductionen_GB
dc.subject.meshToll-Like Receptorsen_GB
dc.subject.meshTumor Necrosis Factor-alphaen_GB
dc.titleViral mediated redirection of NEMO/IKKγ to autophagosomes curtails the inflammatory cascade.en
dc.typeArticleen
dc.contributor.departmentHeinrich Pette Institute, Leibniz Institute for Experimental Virology, Hamburg, Germany.en_GB
dc.identifier.journalPLoS pathogensen_GB

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