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Interferon-inducible antiviral protein MxA enhances cell death triggered by endoplasmic reticulum stress

Akiko Numajiri Haruki1, Tadasuke Naito, Tomomi Nishie

  • 1Department of Infection Biology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Japan.

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
|October 14, 2011
PubMed

Insights

Human myxovirus resistance gene A (MxA) enhances endoplasmic reticulum (ER) stress signaling during influenza virus infection. This MxA-driven ER stress accelerates cell death, contributing to the antiviral defense mechanism.

Area of Science:

  • Virology
  • Cell Biology
  • Immunology

Background:

  • Human myxovirus resistance gene A (MxA) is a type I interferon-inducible protein with known antiviral activity against RNA viruses like influenza.
  • Influenza virus infection, like other viral infections, can induce endoplasmic reticulum (ER) stress, a known pathway for initiating cell death.
  • Previous research established that MxA accelerates the death of influenza-infected cells via caspase-dependent and -independent pathways.

Purpose of the Study:

  • To investigate the role of MxA in ER stress signaling during influenza virus infection.
  • To determine if MxA enhances ER stress and its downstream effects on cell death.

Main Methods:

  • Influenza virus infection of cells expressing MxA.
  • Treatment with tunicamycin (TM), an ER stress inducer.
  • Analysis of ER stress markers, including BiP mRNA expression and XBP1 mRNA processing.
  • Assessment of MxA's interaction with BiP.
  • Evaluation of the effect of BiP overexpression on MxA-promoted ER stress.

Main Results:

  • MxA expression enhanced ER stress signaling in influenza virus-infected cells.
  • ER stress markers (BiP mRNA, XBP1 mRNA processing) were upregulated in MxA-expressing cells upon TM treatment or viral infection.
  • MxA accelerated TM-induced cell death.
  • MxA was found to interact with BiP.
  • Overexpression of BiP attenuated MxA-induced ER stress signaling.

Conclusions:

  • MxA enhances ER stress signaling in influenza virus-infected cells.
  • The interaction between MxA and BiP plays a role in modulating ER stress.
  • MxA-enhanced ER stress signaling contributes to accelerated cell death, likely as an antiviral mechanism.

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