TRADD protein is an essential component of the RIG-like helicase antiviral pathway

Marie-Cécile Michallet; Etienne Meylan; Maria A Ermolaeva; Jessica Vazquez; Manuele Rebsamen; Joseph Curran; Hendrik Poeck; Michael Bscheider; Gunther Hartmann; Martin König; Ulrich Kalinke; Manolis Pasparakis; Jürg Tschopp

doi:10.1016/j.immuni.2008.03.013

TRADD protein is an essential component of the RIG-like helicase antiviral pathway

Immunity. 2008 May;28(5):651-61. doi: 10.1016/j.immuni.2008.03.013. Epub 2008 Apr 24.

Authors

Marie-Cécile Michallet¹, Etienne Meylan, Maria A Ermolaeva, Jessica Vazquez, Manuele Rebsamen, Joseph Curran, Hendrik Poeck, Michael Bscheider, Gunther Hartmann, Martin König, Ulrich Kalinke, Manolis Pasparakis, Jürg Tschopp

Affiliation

¹ Department of Biochemistry, University of Lausanne, Chemin des Boveresses 155, CH-1066 Epalinges, Switzerland.

PMID: 18439848
DOI: 10.1016/j.immuni.2008.03.013

Abstract

Upon detection of viral RNA, the helicases RIG-I and/or MDA5 trigger, via their adaptor Cardif (also known as IPS-1, MAVS, or VISA), the activation of the transcription factors NF-kappaB and IRF3, which collaborate to induce an antiviral type I interferon (IFN) response. FADD and RIP1, known as mediators of death-receptor signaling, are implicated in this antiviral pathway; however, the link between death-receptor and antiviral signaling is not known. Here we showed that TRADD, a crucial adaptor of tumor necrosis factor receptor (TNFRI), was important in RIG-like helicase (RLH)-mediated signal transduction. TRADD is recruited to Cardif and orchestrated complex formation with the E3 ubiquitin ligase TRAF3 and TANK and with FADD and RIP1, leading to the activation of IRF3 and NF-kappaB. Loss of TRADD prevented Cardif-dependent activation of IFN-beta, reduced the production of IFN-beta in response to RNA viruses, and enhanced vesicular stomatitis virus replication. Thus, TRADD is not only an essential component of proinflammatory TNFRI signaling, but is also required for RLH-Cardif-dependent antiviral immune responses.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adaptor Proteins, Signal Transducing / metabolism
Animals
DNA Helicases / metabolism*
Fas-Associated Death Domain Protein / metabolism
GTPase-Activating Proteins / metabolism
Humans
Interferon Regulatory Factor-3 / immunology
Interferon Regulatory Factor-3 / metabolism*
Interferon Type I / immunology
Interferon Type I / metabolism
Membrane Proteins / metabolism
Mice
Mice, Knockout
Mice, Mutant Strains
NF-kappa B / metabolism
Nerve Tissue Proteins / metabolism
Receptors, Cell Surface
Rhabdoviridae Infections / immunology*
Rhabdoviridae Infections / virology
Signal Transduction
TNF Receptor-Associated Death Domain Protein / metabolism*
TNF Receptor-Associated Factor 3 / immunology
TNF Receptor-Associated Factor 3 / metabolism
Ubiquitin-Protein Ligases / metabolism
Vesiculovirus / immunology*
Vesiculovirus / physiology

Substances

Adaptor Proteins, Signal Transducing
Fadd protein, mouse
Fas-Associated Death Domain Protein
GTPase-Activating Proteins
IRF3 protein, human
Interferon Regulatory Factor-3
Interferon Type I
Membrane Proteins
NF-kappa B
Nerve Tissue Proteins
Ralbp1 protein, mouse
Receptors, Cell Surface
Robo3 protein, mouse
TNF Receptor-Associated Death Domain Protein
TNF Receptor-Associated Factor 3
Tank protein, mouse
Ubiquitin-Protein Ligases
DNA Helicases