tetano
Editor, Senior Moderator
Cell Rep. 2015 Mar 11. pii: S2211-1247(15)00176-X. doi: 10.1016/j.celrep.2015.02.030. [Epub ahead of print]
[h=1]MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation and Type I Interferon Response.[/h] James SJ[SUP]1[/SUP], Jiao H[SUP]1[/SUP], Teh HY[SUP]1[/SUP], Takahashi H[SUP]2[/SUP], Png CW[SUP]1[/SUP], Phoon MC[SUP]3[/SUP], Suzuki Y[SUP]3[/SUP], Sawasaki T[SUP]4[/SUP], Xiao H[SUP]5[/SUP], Chow VT[SUP]3[/SUP], Yamamoto N[SUP]3[/SUP], Reynolds JM[SUP]6[/SUP], Flavell RA[SUP]7[/SUP], Dong C[SUP]8[/SUP], Zhang Y[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 25772359 [PubMed - as supplied by publisher]
[h=1]MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation and Type I Interferon Response.[/h] James SJ[SUP]1[/SUP], Jiao H[SUP]1[/SUP], Teh HY[SUP]1[/SUP], Takahashi H[SUP]2[/SUP], Png CW[SUP]1[/SUP], Phoon MC[SUP]3[/SUP], Suzuki Y[SUP]3[/SUP], Sawasaki T[SUP]4[/SUP], Xiao H[SUP]5[/SUP], Chow VT[SUP]3[/SUP], Yamamoto N[SUP]3[/SUP], Reynolds JM[SUP]6[/SUP], Flavell RA[SUP]7[/SUP], Dong C[SUP]8[/SUP], Zhang Y[SUP]9[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] 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.
Copyright ? 2015 The Authors. Published by Elsevier Inc. All rights reserved.
PMID: 25772359 [PubMed - as supplied by publisher]