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Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif
Author(s) -
Saha Supriya K,
Pietras Eric M,
He Jeannie Q,
Kang Jason R,
Liu SuYang,
Oganesyan Gagik,
Shahangian Arash,
Zarnegar Brian,
Shiba Travis L,
Wang Yao,
Cheng Genhong
Publication year - 2006
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1038/sj.emboj.7601220
Subject(s) - biology , microbiology and biotechnology , computational biology
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 IFNα 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.