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Involvement of GRIM-19 in apoptosis induced in H5N1 virus-infected human macrophages

Peeraya Ekchariyawat1, Arunee Thitithanyanont, Stitaya Sirisinha

  • 1Department of Microbiology, Faculty of Science, Mahidol University, Bangkok, Thailand.

Innate Immunity
|March 27, 2013
PubMed

Insights

The H5N1 virus induces cell death by up-regulating the GRIM-19 gene in macrophages. Suppressing GRIM-19 reduces H5N1-induced apoptosis, revealing a key mechanism in viral pathogenesis.

Area of Science:

  • Virology
  • Immunology
  • Cell Biology

Background:

  • H5N1 influenza virus infection is often fatal, with high mortality rates.
  • Viral-induced apoptosis is a key factor in H5N1 pathogenesis, but its molecular mechanisms are not fully understood.

Purpose of the Study:

  • To investigate the molecular mechanisms underlying H5N1-induced apoptosis in human monocyte-derived macrophages (hMDMs).
  • To identify novel genes involved in the apoptotic pathway triggered by H5N1 infection.

Main Methods:

  • Assessing GRIM-19 gene expression in H5N1-infected hMDMs.
  • Evaluating apoptosis levels in GRIM-19 depleted hMDMs post-H5N1 infection.
  • Measuring BH3-interacting domain death agonist cleavage and apoptosis-inducing factor (AIF) release.
  • Investigating the role of Interferon-beta (IFN-β) in regulating GRIM-19 expression.

Main Results:

  • H5N1 virus up-regulates the expression of the gene associated with retinoid and interferon induced mortality-19 (GRIM-19) in hMDMs.
  • Depletion of GRIM-19 significantly reduces H5N1-induced apoptosis, BH3-interacting domain death agonist cleavage, and AIF release.
  • Neutralizing IFN-β antibodies suppress GRIM-19 expression and decrease apoptosis in infected cells.
  • IFN-β secreted by infected hMDMs plays a crucial role in regulating GRIM-19 expression and subsequent apoptosis.

Conclusions:

  • GRIM-19 is a key mediator of H5N1-induced apoptosis in hMDMs.
  • The IFN-β/GRIM-19 signaling pathway is critical for H5N1 viral pathogenesis.
  • This study elucidates a novel regulatory mechanism of H5N1-induced cell death.
Keywords:
ApoptosisGRIM-19H5N1IFN-βinfluenza

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