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Dissecting Innate Immune Signaling in Viral Evasion of Cytokine Production
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Structural basis for the prion-like MAVS filaments in antiviral innate immunity

Hui Xu1, Xiaojing He, Hui Zheng

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

Elife
|February 27, 2014
PubMed

Insights

Mitochondrial antiviral signaling (MAVS) protein forms left-handed helical filaments essential for innate immunity against RNA viruses. These structures, revealed by cryo-EM, clarify MAVS polymerization and antiviral signaling mechanisms.

Area of Science:

  • Structural biology
  • Immunology
  • Virology

Background:

  • Mitochondrial antiviral signaling (MAVS) protein is crucial for innate immune responses against RNA viruses.
  • MAVS forms prion-like aggregates to activate antiviral signaling, but its structural basis remains unclear.

Purpose of the Study:

  • To elucidate the structural mechanism of MAVS polymerization.
  • To understand how MAVS filaments activate antiviral signaling cascades.

Main Methods:

  • Cryo-electron microscopy (cryo-EM) to determine the structures of MAVS CARD and truncated MAVS filaments.
  • Point mutations to investigate the role of specific interfaces in filament formation and function.
  • Super-resolution imaging in virus-infected cells to visualize MAVS clusters.

Main Results:

  • Determined cryo-EM structures of left-handed three-stranded helical filaments formed by MAVS CARD and truncated MAVS.
  • Identified specific electrostatic and hydrophobic interactions at subunit interfaces critical for filament stability.
  • Demonstrated that mutations disrupting these interfaces impair MAVS filament formation and antiviral signaling.
  • Observed rod-shaped MAVS clusters on mitochondria in virus-infected cells.

Conclusions:

  • Elucidated the structural mechanism underlying MAVS polymerization into helical filaments.
  • Explained how distinct chemical interactions within the α-helical domain drive self-perpetuating filament formation.
  • Provided structural insights into the activation of innate antiviral signaling pathways by MAVS.
Keywords:
MAVScryoEM reconstructioninnate immunityprion-like filamentsthree-stranded filaments

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