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Sendai virus C protein limits NO production in infected RAW264.7 macrophages

Erdenezaya Odkhuu1, Takayuki Komatsu2, Naoki Koide2

  • 11 Department of Anatomy, Mongolian National University of Medical Sciences, Mongolia.

Innate Immunity
|September 8, 2018
PubMed

Insights

Sendai virus (SeV) accessory protein C suppresses nitric oxide (NO) production by inhibiting NF-κB activation. This mechanism helps viruses overcome the host

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • Macrophages produce nitric oxide (NO) to inhibit viral replication.
  • Viruses have evolved mechanisms to overcome this NO-mediated defense.

Purpose of the Study:

  • To investigate the role of Sendai virus (SeV) accessory protein C in modulating NO production by infected macrophages.
  • To elucidate the molecular pathways involved in SeV's interaction with host NO synthesis.

Main Methods:

  • Utilized wild-type SeV (wtSeV) and a C protein-deficient mutant (4C(-)) in RAW264.7 murine macrophages.
  • Assessed inducible NO synthase (iNOS) expression and NO production.
  • Investigated the involvement of interferon-beta (IFN-β), JAK-STAT, and NF-κB signaling pathways.
  • Employed cells expressing influenza virus NS1 protein to block double-stranded RNA (dsRNA) signaling.

Main Results:

  • SeV 4C(-) infection significantly enhanced iNOS expression and NO production compared to wtSeV.
  • 4C(-) infection induced marked IFN-β production, contributing to iNOS expression via JAK-STAT.
  • NF-κB activation was observed with 4C(-) infection but not wtSeV.
  • NO production and iNOS induction by 4C(-) were suppressed in cells expressing NS1 protein, indicating a role for dsRNA sensing.

Conclusions:

  • SeV accessory protein C suppresses NF-κB activation, thereby inhibiting iNOS expression and NO production.
  • This suppression mechanism likely involves limiting dsRNA generation during infection.
  • Protein C plays a crucial role in viral evasion of host NO-mediated antiviral responses.
Keywords:
Accessory proteinsNOdouble-stranded RNAmacrophagesparamyxovirus

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