The RNA helicase DHX16 recognizes specific viral RNA to trigger RIG-I-dependent innate antiviral immunity.
DHX16
RIG-I
SARS-CoV-2
TRIM6
influenza A virus
innate immunity
splicing
tripartite motif (TRIM) protein
type I interferon
unanchored ubiquitin
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
08 03 2022
08 03 2022
Historique:
received:
24
04
2021
revised:
02
11
2021
accepted:
02
02
2022
entrez:
9
3
2022
pubmed:
10
3
2022
medline:
17
3
2022
Statut:
ppublish
Résumé
Type I interferons (IFN-I) are essential to establish antiviral innate immunity. Unanchored (or free) polyubiquitin (poly-Ub) has been shown to regulate IFN-I responses. However, few unanchored poly-Ub interactors are known. To identify factors regulated by unanchored poly-Ub in a physiological setting, we developed an approach to isolate unanchored poly-Ub from lung tissue. We identified the RNA helicase DHX16 as a potential pattern recognition receptor (PRR). Silencing of DHX16 in cells and in vivo diminished IFN-I responses against influenza virus. These effects extended to members of other virus families, including Zika and SARS-CoV-2. DHX16-dependent IFN-I production requires RIG-I and unanchored K48-poly-Ub synthesized by the E3-Ub ligase TRIM6. DHX16 recognizes a signal in influenza RNA segments that undergo splicing and requires its RNA helicase motif for direct, high-affinity interactions with specific viral RNAs. Our study establishes DHX16 as a PRR that partners with RIG-I for optimal activation of antiviral immunity requiring unanchored poly-Ub.
Identifiants
pubmed: 35263596
pii: S2211-1247(22)00161-9
doi: 10.1016/j.celrep.2022.110434
pmc: PMC8903195
pii:
doi:
Substances chimiques
Interferon Type I
0
RNA, Viral
0
Receptors, Immunologic
0
Tripartite Motif Proteins
0
DHX16 protein, human
EC 2.7.7.-
RIGI protein, human
EC 3.6.1.-
DEAD Box Protein 58
EC 3.6.4.13
RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
110434Subventions
Organisme : NIAID NIH HHS
ID : R01 AI166668
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI155466
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI132479
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI134907
Pays : United States
Organisme : NIAID NIH HHS
ID : R21 AI126012
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007526
Pays : United States
Organisme : NICHD NIH HHS
ID : K12 HD052023
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI150585
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143292
Pays : United States
Organisme : NIAID NIH HHS
ID : F31 AI152422
Pays : United States
Organisme : NIAID NIH HHS
ID : P01 AI063302
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001439
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI060549
Pays : United States
Organisme : NIAID NIH HHS
ID : P50 AI150476
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of interests The García-Sastre laboratory received research support from Pfizer, Senhwa Biosciences, Kenall Manufacturing, Avimex, Johnson & Johnson, Dynavax, 7 Hills Pharma, PharmaMar, ImmunityBio, Accurius, nanoComposix, Hexamer, N-fold LLC, Model Medicines, Atea Pharma, and Merck. The Krogan laboratory received research support from Vir Biotechnology and F. Hoffmann-La Roche. All declarations of interest are outside of the reported work. All remaining authors declare no competing interests.
Références
Immunity. 2012 Jun 29;36(6):959-73
pubmed: 22705106
J Virol. 1986 Mar;57(3):729-37
pubmed: 3005623
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20209-14
pubmed: 19088201
Proc Natl Acad Sci U S A. 2020 Apr 7;117(14):8094-8103
pubmed: 32198201
Nat Rev Immunol. 2020 Sep;20(9):537-551
pubmed: 32203325
Annu Rev Virol. 2015 Nov;2(1):265-88
pubmed: 26958916
Curr Opin Virol. 2011 Dec;1(6):519-25
pubmed: 22328912
Curr Opin Struct Biol. 2010 Jun;20(3):313-24
pubmed: 20456941
Vaccines (Basel). 2017 Aug 22;5(3):
pubmed: 28829373
EMBO J. 1994 Feb 15;13(4):879-87
pubmed: 8112301
Am J Hum Genet. 2019 Aug 1;105(2):302-316
pubmed: 31256877
Cell. 2006 Mar 24;124(6):1197-208
pubmed: 16564012
J Mol Biol. 2010 Mar 5;396(4):949-66
pubmed: 20026132
Crit Rev Biochem Mol Biol. 2017 Aug;52(4):425-460
pubmed: 28524749
Nat Immunol. 2021 Jul;22(7):820-828
pubmed: 33976430
J Virol. 2008 Jan;82(1):335-45
pubmed: 17942531
Nature. 2007 Apr 19;446(7138):916-920
pubmed: 17392790
Biochem J. 2010 Jul 1;429(1):25-32
pubmed: 20423332
Virology. 2005 Sep 1;339(2):200-12
pubmed: 16002117
J Biochem. 1996 Jul;120(1):160-9
pubmed: 8864859
Biochim Biophys Acta. 2013 Aug;1829(8):854-65
pubmed: 23567047
Cytokine Growth Factor Rev. 2014 Oct;25(5):563-76
pubmed: 25172371
BMC Bioinformatics. 2013 Apr 15;14:128
pubmed: 23586463
J Virol. 2020 Nov 9;94(23):
pubmed: 32938761
Immunity. 2014 Jun 19;40(6):880-95
pubmed: 24882218
Immunity. 2009 Jul 17;31(1):25-34
pubmed: 19576794
Nature. 2020 Sep;585(7825):414-419
pubmed: 32641828
J Virol. 2005 Jun;79(12):7535-43
pubmed: 15919908
mBio. 2021 Feb 16;12(1):
pubmed: 33593976
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Biol Chem. 2010 Nov 12;285(46):35624-32
pubmed: 20841358
Genes Dev. 2015 Jan 1;29(1):94-107
pubmed: 25561498
Annu Rev Immunol. 2018 Apr 26;36:667-694
pubmed: 29677479
J Virol. 2020 Jun 16;94(13):
pubmed: 32295922
Nat Methods. 2010 Dec;7(12):1009-15
pubmed: 21057496
mBio. 2014 May 13;5(3):e00070-14
pubmed: 24825008
Mol Cell Biol. 1996 Dec;16(12):6810-9
pubmed: 8943336
J Immunol. 2014 Aug 1;193(3):1364-72
pubmed: 24990078
Nat Protoc. 2014 Nov;9(11):2663-81
pubmed: 25321410
J Virol. 2017 Mar 29;91(8):
pubmed: 28148787
Nature. 2009 Sep 3;461(7260):114-9
pubmed: 19675569
Cell. 2010 Feb 5;140(3):397-408
pubmed: 20144762
Immunity. 2013 Jul 25;39(1):123-35
pubmed: 23871209
Mol Cell Biol. 2011 Sep;31(18):3802-19
pubmed: 21791617
PLoS Pathog. 2014 Mar 20;10(3):e1004012
pubmed: 24651521
Cell. 2010 Apr 16;141(2):315-30
pubmed: 20403326
Sci Rep. 2016 Jul 08;6:29263
pubmed: 27387525
J Virol. 2020 Jan 6;94(2):
pubmed: 31694946
Mol Cell. 2001 Aug;8(2):251-62
pubmed: 11545728
Nat Immunol. 2011 Sep 04;12(10):959-65
pubmed: 21892174
Elife. 2017 Jan 16;6:
pubmed: 28092261
Cell Rep. 2018 Jul 10;24(2):320-328
pubmed: 29996094
RNA. 2000 Aug;6(8):1106-19
pubmed: 10943890
Cell Host Microbe. 2020 May 13;27(5):841-848.e3
pubmed: 32289263
PLoS Pathog. 2016 Sep 13;12(9):e1005880
pubmed: 27622505
Genomics. 2003 Jun;81(6):618-22
pubmed: 12782131
Cell Rep. 2020 Oct 6;33(1):108234
pubmed: 32979938
Cell. 2006 Feb 24;124(4):783-801
pubmed: 16497588
J Virol. 2021 Jan 29;:
pubmed: 33514628
J Virol. 2017 Aug 24;91(18):
pubmed: 28679761
J Gen Virol. 2019 Dec;100(12):1641-1662
pubmed: 31661051
Bioinformatics. 2013 Jan 1;29(1):15-21
pubmed: 23104886
PLoS Pathog. 2021 Jan 19;17(1):e1009226
pubmed: 33465137
J Virol. 2011 May;85(10):4963-73
pubmed: 21389138
J Virol. 2003 Dec;77(24):13257-66
pubmed: 14645582
J Virol. 2020 Dec 2;:
pubmed: 33268519
J Control Release. 2006 Dec 1;116(3):304-13
pubmed: 17097177
Immunity. 2020 Jul 14;53(1):26-42
pubmed: 32668226
Immunity. 2011 Jun 24;34(6):866-78
pubmed: 21703541
Sci Signal. 2014 Apr 29;7(323):ra40
pubmed: 24782566
Cell Host Microbe. 2016 Jun 8;19(6):891-900
pubmed: 27198478
Nat Rev Mol Cell Biol. 2011 Jul 22;12(8):505-16
pubmed: 21779027
Nature. 2011 Apr 21;472(7343):361-5
pubmed: 21512573
Nucleic Acids Res. 2016 Jul 8;44(W1):W90-7
pubmed: 27141961
Acta Crystallogr D Struct Biol. 2018 Jul 1;74(Pt 7):643-654
pubmed: 29968674
J Mol Biol. 2014 Mar 20;426(6):1265-84
pubmed: 24333484
Proc Natl Acad Sci U S A. 2014 May 27;111(21):7747-52
pubmed: 24821782
J Immunol. 2011 Nov 1;187(9):4501-8
pubmed: 21957149
EMBO J. 1994 Feb 15;13(4):888-97
pubmed: 8112302
Methods Mol Biol. 2017;1565:191-199
pubmed: 28364244
Biosci Rep. 2014 Dec 12;34(6):e00163
pubmed: 25296192
Mol Cell Biol. 2006 Feb;26(4):1195-208
pubmed: 16449635
J Virol. 2015 Jun;89(11):6067-79
pubmed: 25810557
Viruses. 2020 Dec 30;13(1):
pubmed: 33396605
J Interferon Cytokine Res. 2019 Jun;39(6):331-346
pubmed: 31090472
Curr Clin Microbiol Rep. 2020;7(4):101-114
pubmed: 32837832
Cell. 2004 Oct 29;119(3):381-92
pubmed: 15507209
Cell Mol Immunol. 2014 Jan;11(1):49-57
pubmed: 24037184
Science. 2006 Nov 10;314(5801):994-7
pubmed: 17038590
Immunity. 2011 May 27;34(5):680-92
pubmed: 21616437
EMBO J. 2001 May 1;20(9):2140-51
pubmed: 11331580
PLoS Pathog. 2018 Feb 20;14(2):e1006886
pubmed: 29462185
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20203-8
pubmed: 19088196
Cell Rep. 2021 Jan 12;34(2):108628
pubmed: 33440148
J Biol Chem. 2010 Jun 25;285(26):20252-61
pubmed: 20406818
Proc Natl Acad Sci U S A. 2010 Jun 22;107(25):11531-6
pubmed: 20534532