title: A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance.
abstract: Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus.
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, USA.
authors: K A
authors: KA
authors: Gabor
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA.
authors: J R
authors: JR
authors: Charette
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA.
authors: M J
authors: MJ
authors: Pietraszewski
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA.
authors: D J
authors: DJ
authors: Wingfield
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA.
authors: J S
authors: JS
authors: Shim
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, USA.
authors: P J
authors: PJ
authors: Millard
authors: Department of Molecular and Biomedical Sciences, University of Maine, Orono, ME, USA; Graduate School of Biomedical Science and Engineering, University of Maine, Orono, ME, USA. Electronic address: carolkim@maine.edu.
authors: C H
authors: CH
authors: Kim
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D007110:Immunity, Active / Q000235:genetics; D007370:Interferon Type I / Q000378:metabolism; D009154:Mutation / Q000235:genetics; D051192:Receptors, Pattern Recognition / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012209:Rhabdoviridae / Q000276:immunology*; D018353:Rhabdoviridae Infections / Q000276:immunology*; D019076:Transgenes / Q000235:genetics; D019562:Viral Load / Q000235:genetics; D015027:Zebrafish / Q000276:immunology*; D029961:Zebrafish Proteins / Q000235:genetics / Q000276:immunology / Q000378:metabolism*
chemical_list: D007370:Interferon Type I; D051192:Receptors, Pattern Recognition; D029961:Zebrafish Proteins; C586913:MDA5 protein,zebrafish; D053487:DEAD-box RNA Helicases
keywords: Antiviral; Danio rerio; Mda5; Rhabdovirus; Type I IFN; Zebrafish
references: Proc Natl Acad Sci U S A. 2010 Sep 14;107(37):16303-8
references: 20805493
references: Arch Biochem Biophys. 2009 Aug 1;488(1):23-33
references: 19531363
references: Curr Drug Targets. 2011 Jun;12(7):1000-17
references: 21366518
references: Immunity. 2011 May 27;34(5):680-92
references: 21616437
references: J Virol. 2011 Aug;85(16):8403-12
references: 21680521
references: Nat Biotechnol. 2011 Aug;29(8):699-700
references: 21822242
references: Cell. 2011 Oct 14;147(2):409-22
references: 22000018
references: Cell. 2011 Oct 14;147(2):423-35
references: 22000019
references: Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21010-5
references: 22160685
references: Dev Comp Immunol. 2012 Jul;37(3-4):381-9
references: 22387588
references: PLoS One. 2012;7(10):e47737
references: 23091644
references: J Biol Chem. 2012 Dec 14;287(51):42564-73
references: 23055530
references: J Virol. 2009 Aug;83(16):7815-27
references: 19474100
references: J Immunol. 2014 May 1;192(9):4328-41
references: 24683187
references: J Immunol. 2009 Nov 1;183(9):5896-908
references: 19812203
references: Fish Shellfish Immunol. 2010 Apr;28(4):712-8
references: 20109556
references: Future Microbiol. 2010 Apr;5(4):563-9
references: 20353298
references: J Neurovirol. 2008 Nov;14(6):503-13
references: 18991139
references: Nat Struct Mol Biol. 2010 Jul;17(7):781-7
references: 20581823
references: J Fish Dis. 2010 Aug;33(8):701-4
references: 20497291
references: Trends Microbiol. 2014 Sep;22(9):490-7
references: 24865811
references: J Virol. 2014 Nov;88(21):12915-22
references: 25142596
references: Dis Model Mech. 2014 Nov;7(11):1227-37
references: 25190709
references: Dev Comp Immunol. 2015 Jan;48(1):95-101
references: 25265425
references: Fish Shellfish Immunol. 2015 Mar;43(1):13-24
references: 25524497
references: Immunol Rev. 2000 Feb;173:89-97
references: 10719670
references: Proc Natl Acad Sci U S A. 2000 Oct 10;97(21):11403-8
references: 11027340
references: Genes Dev. 1994 Jun 15;8(12):1434-47
references: 7926743
references: Cell Biol Toxicol. 1994 Jun;10(3):167-76
references: 7994634
references: J Virol. 2005 Feb;79(3):1842-52
references: 15650208
references: Mol Immunol. 2005 May;42(9):1057-71
references: 15829296
references: Immunity. 2005 Jul;23(1):19-28
references: 16039576
references: Cell. 2005 Sep 9;122(5):669-82
references: 16125763
references: Mol Cell. 2005 Sep 16;19(6):727-40
references: 16153868
references: Nat Immunol. 2005 Oct;6(10):981-8
references: 16127453
references: Nature. 2006 May 4;441(7089):101-5
references: 16625202
references: Proc Natl Acad Sci U S A. 2006 May 30;103(22):8459-64
references: 16714379
references: Science. 2006 Nov 10;314(5801):994-7
references: 17038590
references: Proc Natl Acad Sci U S A. 2007 Jan 9;104(2):582-7
references: 17190814
references: Nat Rev Neurosci. 2007 Feb;8(2):128-40
references: 17195035
references: J Immunol. 2007 Apr 1;178(7):4385-94
references: 17371995
references: J Immunol. 2007 Apr 1;178(7):4517-27
references: 17372010
references: Dev Dyn. 2007 Nov;236(11):3088-99
references: 17937395
references: J Virol. 2008 Jan;82(1):335-45
references: 17942531
references: Mol Cell. 2008 Feb 29;29(4):428-40
references: 18242112
references: Cell Microbiol. 2008 May;10(5):1027-39
references: 18298637
references: Nat Biotechnol. 2008 Jun;26(6):695-701
references: 18500337
references: J Exp Med. 2008 Jul 7;205(7):1601-10
references: 18591409
references: Fish Shellfish Immunol. 2008 Oct;25(4):341-50
references: 18640057
references: BMC Evol Biol. 2009;9:85
references: 19400936
references: Structure. 2010 Aug 11;18(8):1032-43
references: 20637642
references: Cell. 2013 Jan 17;152(1-2):276-89
references: 23273991
references: Gene. 2013 Mar 10;516(2):320-7
references: 23274655
references: Adv Exp Med Biol. 2013;783:251-66
references: 23468113
references: Nat Biotechnol. 2013 Mar;31(3):227-9
references: 23360964
references: PLoS One. 2013;8(7):e68759
references: 23874753
references: Fish Shellfish Immunol. 2013 Dec;35(6):1689-702
references: 23462146
references: Immunology. 2014 Feb;141(2):192-202
references: 24116956
references: J Mol Biol. 2014 Mar 20;426(6):1351-65
references: 24211720
references: PLoS Pathog. 2011;7(2):e1001269
references: 21304884