title: MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation and Type I Interferon Response.
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.
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Sharmy J
authors.initials: SJ
authors.lastname: James
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Huipeng
authors.initials: H
authors.lastname: Jiao
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Hong-Ying
authors.initials: HY
authors.lastname: Teh
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Takahashi
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore.
authors.forename: Chin Wen
authors.initials: CW
authors.lastname: Png
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore.
authors.forename: Meng Chee
authors.initials: MC
authors.lastname: Phoon
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore.
authors.forename: Youichi
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Proteo-Science Center, Ehime University, Matsuyama, Ehime 790-8577, Japan.
authors.forename: Tatsuy
authors.initials: T
authors.lastname: Sawasaki
authors.affiliation: Unit of Immune Regulation and Signaling, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Xiao
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore.
authors.forename: Vincent T K
authors.initials: VTK
authors.lastname: Chow
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore.
authors.forename: Naoki
authors.initials: N
authors.lastname: Yamamoto
authors.affiliation: Department of Microbiology & Immunology, Chicago Medical School, Rosalind Franklin University of Medicine and Science, Chicago, IL 60064, USA.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Reynolds
authors.affiliation: Department of Immunology, Howard Hughes Medical Institute, Yale University, New Haven, CT 06520, USA.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Flavell
authors.affiliation: Tsinghua University, Beijing 100084, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Dong
authors.affiliation: Department of Microbiology, Yong Loo Lin School of Medicine, Singapore 117597, Singapore; Immunology Progamme, Life Sciences Institute, National University of Singapore, Singapore 117597, Singapore. Electronic address: miczy@nus.edu.sg.
authors.forename: Yongliang
authors.initials: Y
authors.lastname: Zhang