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Title

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

Authors
Michallet, Marie-Cécile
Meylan, Etienne
Ermolaeva, Maria A.
Vazquez, Jessica
Rebsamen, Manuele
Poeck, Hendrik
Bscheider, Michael
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Published in Immunity. 2008, vol. 28, no. 5, p. 651-61
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.
Keywords Adaptor Proteins, Signal Transducing/metabolismAnimalsDNA Helicases/metabolismFas-Associated Death Domain Protein/metabolismGTPase-Activating Proteins/metabolismHumansInterferon Regulatory Factor-3/immunology/metabolismInterferon Type I/immunology/metabolismMembrane Proteins/metabolismMiceMice, KnockoutMice, Mutant StrainsNF-kappa B/metabolismNerve Tissue Proteins/metabolismRhabdoviridae Infections/immunology/virologySignal TransductionTNF Receptor-Associated Death Domain Protein/metabolismTNF Receptor-Associated Factor 3/immunology/metabolismUbiquitin-Protein Ligases/metabolismVesiculovirus/immunology/physiology
Identifiers
PMID: 18439848
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Structures
Research group Régulation traductionnelle dans les cellules de mammifère (631)
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MICHALLET, Marie-Cécile et al. TRADD protein is an essential component of the RIG-like helicase antiviral pathway. In: Immunity, 2008, vol. 28, n° 5, p. 651-61. https://archive-ouverte.unige.ch/unige:1888

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Deposited on : 2009-06-04

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