Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_4FC90177222F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Human cytomegalovirus glycoprotein UL141 targets the TRAIL death receptors to thwart host innate antiviral defenses.
Périodique
Cell Host and Microbe
ISSN
1934-6069 (Electronic)
ISSN-L
1931-3128
Statut éditorial
Publié
Date de publication
2013
Volume
13
Numéro
3
Pages
324-335
Langue
anglais
Résumé
Death receptors (DRs) of the TNFR superfamily contribute to antiviral immunity by promoting apoptosis and regulating immune homeostasis during infection, and viral inhibition of DR signaling can alter immune defenses. Here we identify the human cytomegalovirus (HCMV) UL141 glycoprotein as necessary and sufficient to restrict TRAIL DR function. Despite showing no primary sequence homology to TNF family cytokines, UL141 binds the ectodomains of both human TRAIL DRs with affinities comparable to the natural ligand TRAIL. UL141 binding promotes intracellular retention of the DRs, thus protecting virus infected cells from TRAIL and TRAIL-dependent NK cell-mediated killing. The identification of UL141 as a herpesvirus modulator of the TRAIL DRs strongly implicates this pathway as a regulator of host defense to HCMV and highlights UL141 as a pleiotropic inhibitor of NK cell effector function.
Mots-clé
Cytomegalovirus/genetics, Cytomegalovirus/immunology, Cytomegalovirus Infections/genetics, Cytomegalovirus Infections/immunology, Host-Pathogen Interactions, Humans, Immunity, Innate, Killer Cells, Natural/immunology, Membrane Glycoproteins/genetics, Membrane Glycoproteins/immunology, Protein Binding, Receptors, TNF-Related Apoptosis-Inducing Ligand/genetics, Receptors, TNF-Related Apoptosis-Inducing Ligand/immunology, Viral Proteins/genetics, Viral Proteins/immunology
Pubmed
Web of science
Open Access
Oui
Création de la notice
14/01/2014 15:53
Dernière modification de la notice
30/04/2021 7:10