Arenavirus Nucleoprotein Targets Interferon Regulatory Factor-Activating Kinase IKKε.

Détails

ID Serval
serval:BIB_0FB7BCD1C2F0
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Arenavirus Nucleoprotein Targets Interferon Regulatory Factor-Activating Kinase IKKε.
Périodique
Journal of Virology
Auteur(s)
Pythoud C., Rodrigo W.W., Pasqual G., Rothenberger S., Martínez-Sobrido L., de la Torre J.C., Kunz S.
ISSN
1098-5514 (Electronic)
ISSN-L
0022-538X
Statut éditorial
Publié
Date de publication
2012
Peer-reviewed
Oui
Volume
86
Numéro
15
Pages
7728-7738
Langue
anglais
Notes
Publication types: Journal Article
Résumé
Arenaviruses perturb innate antiviral defense by blocking induction of type I interferon (IFN) production. Accordingly, the arenavirus nucleoprotein (NP) was shown to block activation and nuclear translocation of interferon regulatory factor 3 (IRF3) in response to virus infection. Here, we sought to identify cellular factors involved in innate antiviral signaling targeted by arenavirus NP. Consistent with previous studies, infection with the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV) prevented phosphorylation of IRF3 in response to infection with Sendai virus, a strong inducer of the retinoic acid-inducible gene I (RIG-I)/mitochondrial antiviral signaling (MAVS) pathway of innate antiviral signaling. Using a combination of coimmunoprecipitation and confocal microscopy, we found that LCMV NP associates with the IκB kinase (IKK)-related kinase IKKε but that, rather unexpectedly, LCMV NP did not bind to the closely related TANK-binding kinase 1 (TBK-1). The NP-IKKε interaction was highly conserved among arenaviruses from different clades. In LCMV-infected cells, IKKε colocalized with NP but not with MAVS located on the outer membrane of mitochondria. LCMV NP bound the kinase domain (KD) of IKKε (IKBKE) and blocked its autocatalytic activity and its ability to phosphorylate IRF3, without undergoing phosphorylation. Together, our data identify IKKε as a novel target of arenavirus NP. Engagement of NP seems to sequester IKKε in an inactive complex. Considering the important functions of IKKε in innate antiviral immunity and other cellular processes, the NP-IKKε interaction likely plays a crucial role in arenavirus-host interaction.
Pubmed
Web of science
Open Access
Oui
Création de la notice
27/08/2012 18:14
Dernière modification de la notice
08/05/2019 14:30
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