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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3
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A High Resolution Method to Monitor Phosphorylation-dependent Activation of IRF3

Published on: January 24, 2016

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MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation

Sharmy J James1, Huipeng Jiao1, Hong-Ying Teh1

  • 1Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore.

Cell Reports
|March 17, 2015
PubMed

Insights

Virus infection activates MAPK phosphatase 5 (MKP5), a phosphatase that inhibits antiviral immunity. MKP5 deficiency enhances type I interferon responses, revealing a viral immune evasion strategy.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • The type I interferon system is crucial for antiviral defense.
  • Viruses employ immune evasion strategies to counteract host defenses.
  • MAPK phosphatase 5 (MKP5), a dual-specificity phosphatase (DUSP), is induced during viral infections.

Purpose of the Study:

  • To investigate the role of MKP5 in antiviral immunity.
  • To elucidate the mechanism by which viruses evade type I interferon responses.

Main Methods:

  • Analysis of MKP5 expression in virus-infected host cells.
  • Phenotypic analysis of MKP5-deficient mice infected with H1N1 influenza virus.
  • Assessment of type I interferon responses in MKP5-deficient cells and animals upon infection with various RNA viruses.
  • Investigation of the interaction between MKP5 and IRF3.

Main Results:

  • Virus infection induces MKP5 expression in host cells.
  • MKP5-deficient mice exhibit resistance to H1N1 influenza infection.
  • MKP5 deficiency leads to enhanced IRF3 activation and type I interferon expression.
  • MKP5 directly interacts with and dephosphorylates IRF3, negatively regulating its activity.
  • Enhanced type I interferon responses are observed in MKP5-deficient models upon infection with vesicular stomatitis virus and sendai virus.

Conclusions:

  • MKP5 plays a critical role in the negative regulation of IRF3 activity.
  • Influenza and other RNA viruses utilize MKP5 to inhibit the host's type I interferon response.
  • MKP5 represents a novel target for therapeutic intervention against viral infections.

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