Journal
EMBO JOURNAL
Volume 25, Issue 14, Pages 3257-3263Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.emboj.7601220
Keywords
Cardif; TRAF; interacting motif; TRAF3; type I interferon; virus
Categories
Funding
- NIAID NIH HHS [1R01 AI069120, AI07126-30, R01 AI056154, T32 AI007126, R01 AI069120] Funding Source: Medline
- NIGMS NIH HHS [GM 07185, GM 08042, T32 GM007185, T32 GM008042] Funding Source: Medline
Ask authors/readers for more resources
Upon recognition of viral infection, RIG-I and Helicard recruit a newly identified adapter termed Cardif, which induces type I interferon (IFN)-mediated antiviral responses through an unknown mechanism. Here, we demonstrate that TRAF3, like Cardif, is required for type I interferon production in response to intracellular double-stranded RNA. Cardif-mediated IFN alpha induction occurs through a direct interaction between the TRAF domain of TRAF3 and a TRAF-interaction motif (TIM) within Cardif. Interestingly, while the entire N-terminus of TRAF3 was functionally interchangeable with that of TRAF5, the TRAF domain of TRAF3 was not. Our data suggest that this distinction is due to an inability of the TRAF domain of TRAF5 to bind the TIM of Cardif. Finally, we show that preventing association of TRAF3 with this TIM by mutating two critical amino acids in the TRAF domain also abolishes TRAF3-dependent IFN production following viral infection. Thus, our findings suggest that the direct and specific interaction between the TRAF domain of TRAF3 and the TIM of Cardif is required for optimal Cardif-mediated antiviral responses.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available