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

Cell Reports
Sharmy J JamesYongliang Zhang

Abstract

The type I interferon system is essential for antiviral immune response and is a primary target of viral immune evasion strategies. Here, we show that virus infection induces the expression of MAPK phosphatase 5 (MKP5), a dual-specificity phosphatase (DUSP), in host cells. Mice deficient in MKP5 were resistant to H1N1 influenza infection, which is associated with increased IRF3 activation and type I interferon expression in comparison with WT mice. Increased type I interferon responses were also observed in MKP5-deficient cells and animals upon other RNA virus infection, including vesicular stomatitis virus and sendai virus. These observations were attributed to the ability of MKP5 to interact with and dephosphorylate IRF3. Our study reveals a critical function of a DUSP in negative regulation of IRF3 activity and demonstrates a mechanism by which influenza and other RNA viruses inhibit type I interferon response in the host through MKP5.

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Citations

Jan 8, 2016·Antiviral Research·Sandra SöderholmDenis Kainov
Jun 20, 2016·Cardiovascular Pathology : the Official Journal of the Society for Cardiovascular Pathology·Hui TaoJun Li
Aug 31, 2016·Journal of Molecular and Cellular Cardiology·Ruijie Liu, Jeffery D Molkentin
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May 11, 2016·Immune Network·Heng Boon Low, Yongliang Zhang
Apr 4, 2019·International Journal of Molecular Sciences·Marta Jiménez-MartínezManuel Fresno
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Sep 17, 2020·The EMBO Journal·Kiramage ChathurangaJong-Soo Lee
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Feb 16, 2019·International Journal of Molecular Sciences·Grace C A ManleyYongliang Zhang
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