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Article

  • The EMBO Journal (2006) 25, 3257 - 3263
  • doi:10.1038/sj.emboj.7601220

Published online: 6 July 2006

Regulation of antiviral responses by a direct and specific interaction between TRAF3 and Cardif

Supriya K Saha1,2,a, Eric M Pietras1,a, Jeannie Q He1, Jason R Kang1, Su-Yang Liu2, Gagik Oganesyan1,2, Arash Shahangian1,2, Brian Zarnegar1, Travis L Shiba1, Yao Wang1 and Genhong Cheng1,3

  1. Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, CA, USA
  2. Medical Scientist Training Program, University of California Los Angeles, Los Angeles, CA, USA
  3. Center for Infection and Immunity, Institute of Biophysics, Chinese Academic of Science, Beijing, China

Correspondence to:

Genhong Cheng, Department of Microbiology, Immunology and Molecular Genetics, University of California Los Angeles, Los Angeles, 8-240 Factor Building, 10833 Le Conte Avenue, Los Angeles, CA 90095, USA. Tel.: +1 310 825 8896; Fax: +1 310 206-5553; E-mail: genhongc@microbio.ucla.edu

aThese authors contributed equally to this work

Received 22 February 2006; Accepted 9 June 2006

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 IFNalpha 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.

  • Keywords:

    • Cardif,
    • TRAF-interacting motif,
    • TRAF3,
    • type I interferon,
    • virus