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FAS-associated factor-1 positively regulates type I interferon response to RNA virus infection by targeting NLRX1

Jae-Hoon Kim1, Min-Eun Park1, Chamilani Nikapitiya1

  • 1College of Veterinary Medicine, Chungnam National University, Daejeon, Republic of Korea.

Plos Pathogens
|May 26, 2017
PubMed

Insights

FAS-associated factor-1 (FAF1) is crucial for antiviral defense. It enhances type I interferon production by regulating NLRX1-MAVS interactions, boosting RNA virus resistance.

Area of Science:

  • Immunology
  • Molecular Biology
  • Virology

Background:

  • FAS-associated factor-1 (FAF1) is known to be involved in Fas-mediated apoptosis and NF-κB regulation.
  • The role of FAF1 in innate immune responses, particularly against viral infections, remains largely unexplored.

Purpose of the Study:

  • To investigate the role of FAF1 in the type I interferon pathway and antiviral immunity.
  • To elucidate the molecular mechanism by which FAF1 regulates antiviral signaling.

Main Methods:

  • Utilized FAF1gt/gt mice deficient in FAF1 and FAF1 knockdown immune cells.
  • Assessed susceptibility to RNA virus infection, inflammatory cytokine, and type I interferon production.
  • Investigated protein-protein interactions using co-immunoprecipitation and analyzed signaling pathways.

Main Results:

  • FAF1-deficient mice and immune cells exhibited increased susceptibility to RNA virus infection.
  • Reduced levels of inflammatory cytokines and type I interferon (IFN) were observed in FAF1-deficient models.
  • FAF1 competitively binds NLRX1, disrupting the NLRX1-MAVS complex and promoting MAVS-RIG-I interaction to activate antiviral signaling.

Conclusions:

  • FAF1 plays a critical positive regulatory role in the type I interferon pathway.
  • FAF1 is essential for effective antiviral responses against RNA virus infection by modulating the MAVS-RIG-I signaling cascade.
  • FAF1 acts as a key mediator in innate immunity against viral pathogens.

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