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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
08:32

Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production

Published on: March 2, 2014

MAVS recruits multiple ubiquitin E3 ligases to activate antiviral signaling cascades

Siqi Liu1, Jueqi Chen, Xin Cai

  • 1Department of Molecular Biology , University of Texas Southwestern Medical Center , Dallas , United States.

Elife
|August 17, 2013
PubMed

Insights

RIG-I-like receptors detect RNA viruses, triggering type-I interferons via MAVS. TRAF proteins (TRAF2, TRAF5, TRAF6) are essential for MAVS signaling, activating IRF3 and antiviral immunity.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • RNA virus infections are sensed by RIG-I-like receptors (RLRs).
  • RLRs signal through the mitochondrial adaptor MAVS to induce type-I interferons.
  • MAVS forms prion-like polymers that activate downstream kinases.

Purpose of the Study:

  • To elucidate the mechanism of MAVS-mediated signaling.
  • To identify proteins involved in MAVS polymer activation.
  • To understand the role of TRAF proteins in antiviral immune responses.

Main Methods:

  • Site-directed mutagenesis to disrupt TRAF-binding motifs on MAVS.
  • Analysis of IRF3 activation in wild-type and mutant cells.
  • Assessment of MAVS signaling in TRAF-deficient cells.
  • Investigation of ubiquitination events and kinase activation.

Main Results:

  • MAVS polymers recruit TRAF2, TRAF5, and TRAF6 via specific binding motifs.
  • Disruption of MAVS-TRAF interactions abrogates IRF3 activation.
  • TRAF2, 5, and 6 are essential for MAVS-induced IRF3 activation.
  • TRAF proteins facilitate NEMO recruitment and activation of IKK and TBK1 kinases.

Conclusions:

  • TRAF2, TRAF5, and TRAF6 are critical components of the MAVS signaling pathway.
  • These TRAF proteins mediate IRF3 activation, crucial for antiviral immunity.
  • The study reveals a novel role for TRAF proteins in RLR signaling beyond NF-κB activation.
Keywords:
HumanMAVSMouseVirusesinnate immunitymitochondriasignalingubiquitinvirus

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