title: Heat shock cognate 71 (HSC71) regulates cellular antiviral response by impairing formation of VISA aggregates.
abstract: In response to viral infection, RIG-I-like RNA helicases detect viral RNA and signal through the mitochondrial adapter protein VISA. VISA activation leads to rapid activation of transcription factors IRF3 and NF-κB, which collaborate to induce transcription of type I interferon (IFN) genes and cellular antiviral response. It has been demonstrated that VISA is activated by forming prion-like aggregates. However, how this process is regulated remains unknown. Here we show that overexpression of HSC71 resulted in potent inhibition of virus-triggered transcription of IFNB1 gene and cellular antiviral response. Consistently, knockdown of HSC71 had opposite effects. HSC71 interacted with VISA, and negatively regulated virus-triggered VISA aggregation. These findings suggest that HSC71 functions as a check against VISA-mediated antiviral response.
authors: College of Life Sciences, Wuhan University, Wuhan 430072, China.
authors: Zhigang
authors: Z
authors: Liu
authors: Shu-Wen
authors: SW
authors: Wu
authors: Cao-Qi
authors: CQ
authors: Lei
authors: Qian
authors: Q
authors: Zhou
authors: Shu
authors: S
authors: Li
authors: Hong-Bing
authors: HB
authors: Shu
authors: Yan-Yi
authors: YY
authors: Wang
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis* / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D002449:Cell Aggregation / Q000235:genetics; D058851:GPI-Linked Proteins / Q000378:metabolism; D055785:Gene Knockdown Techniques; D057809:HEK293 Cells; D050883:HSC70 Heat-Shock Proteins / Q000235:genetics* / Q000378:metabolism; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D050838:Interferon Regulatory Factor-3 / Q000235:genetics / Q000378:metabolism; D016899:Interferon-beta / Q000235:genetics; D016328:NF-kappa B / Q000235:genetics; D011328:Prions / Q000378:metabolism; D018168:Receptors, Retinoic Acid / Q000378:metabolism; D014780:Viruses / Q000187:drug effects / Q000378:metabolism* / Q000472:pathogenicity
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D058851:GPI-Linked Proteins; D050883:HSC70 Heat-Shock Proteins; C494371:HSPA8 protein, human; C494232:IRF3 protein, human; D050838:Interferon Regulatory Factor-3; C505371:MAVS protein, human; D016328:NF-kappa B; C437968:PLAAT4 protein, human; C501125:PRND protein, human; D011328:Prions; D018168:Receptors, Retinoic Acid; D016899:Interferon-beta
references: J Biol Chem. 2010 Mar 26;285(13):9470-9476
references: 20097753
references: PLoS Pathog. 2009 Nov;5(11):e1000650
references: 19893624
references: Proc Natl Acad Sci U S A. 2011 Nov 29;108(48):19341-6
references: 22084099
references: Proc Natl Acad Sci U S A. 2010 Jan 12;107(2):815-20
references: 20080758
references: Biochem Soc Trans. 2004 Aug;32(Pt 4):636-9
references: 15270695
references: Proc Natl Acad Sci U S A. 2004 Dec 7;101(49):17264-9
references: 15563593
references: Cell. 2006 Feb 24;124(4):783-801
references: 16497588
references: Nat Immunol. 2005 Oct;6(10):981-8
references: 16127453
references: Nat Immunol. 2004 Jul;5(7):730-7
references: 15208624
references: Eur J Immunol. 2010 Jun;40(6):1541-4
references: 20468008
references: Curr Opin Immunol. 2002 Feb;14(1):45-51
references: 11790532
references: J Immunol. 2011 Sep 1;187(5):2559-68
references: 21813773
references: Cell Host Microbe. 2012 Aug 16;12(2):129-31
references: 22901534
references: Immunity. 2010 Dec 14;33(6):878-89
references: 21145761
references: Immunity. 1998 Jun;8(6):657-65
references: 9655479
references: Immunity. 2008 Oct 17;29(4):538-50
references: 18818105
references: Proc Natl Acad Sci U S A. 2007 Aug 28;104(35):14050-5
references: 17709747
references: Nature. 2008 Jan 31;451(7178):573-7
references: 18200010
references: Mol Cell. 2005 Sep 16;19(6):727-40
references: 16153868
references: Sci Signal. 2009 Aug 18;2(84):ra47
references: 19690333
references: Proc Natl Acad Sci U S A. 2009 May 12;106(19):7945-50
references: 19416887
references: Nat Immunol. 2009 Dec;10(12):1300-8
references: 19881509
references: Cell. 2005 Sep 9;122(5):669-82
references: 16125763
references: J Immunol. 2009 Oct 1;183(7):4241-8
references: 19734229
references: Proc Natl Acad Sci U S A. 2012 Aug 28;109(35):14128-33
references: 22904187
references: Immunity. 2009 Mar 20;30(3):397-407
references: 19285439
references: Cell. 2010 Apr 16;141(2):315-30
references: 20403326
references: Proc Natl Acad Sci U S A. 2009 Feb 3;106(5):1530-5
references: 19164550
references: Cell Mol Immunol. 2004 Aug;1(4):274-9
references: 16225770
references: Immunity. 2011 Jun 24;34(6):854-65
references: 21703540
references: Proc Natl Acad Sci U S A. 2012 Jul 17;109(29):11770-5
references: 22745163
references: PLoS One. 2010 Feb 11;5(2):e9172
references: 20161788
references: J Biol Chem. 2011 May 6;286(18):15883-94
references: 21454478
references: Nature. 2005 Oct 20;437(7062):1167-72
references: 16177806
references: Cell. 2011 Aug 5;146(3):448-61
references: 21782231