LYAR Suppresses Beta Interferon Induction by Targeting Phosphorylated Interferon Regulatory Factor 3.
A549 Cells
DNA-Binding Proteins
/ genetics
Gene Expression Regulation
HEK293 Cells
Humans
Immunity, Innate
Interferon Regulatory Factor-3
/ genetics
Interferon-beta
/ genetics
Mutation
Nuclear Proteins
/ genetics
Phosphorylation
Promoter Regions, Genetic
Protein Binding
Signal Transduction
/ immunology
Virus Diseases
/ immunology
Virus Replication
Viruses
/ classification
IFN-β
IRF3
LYAR
innate immune responses
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
01 11 2019
01 11 2019
Historique:
received:
07
05
2019
accepted:
08
08
2019
pubmed:
16
8
2019
medline:
17
6
2020
entrez:
16
8
2019
Statut:
epublish
Résumé
The innate immune response is vital for host defense and must be tightly controlled, but the mechanisms responsible for its negative regulation are not fully understood. The cell growth-regulating nucleolar protein LYAR was found to promote replication of multiple viruses in our previous study. Here, we report that LYAR acts as a negative regulator of innate immune responses. We found that LYAR expression is induced by beta interferon (IFN-β) during virus infection. Further studies showed that LYAR interacts with phosphorylated IFN regulatory factor 3 (IRF3) to impede the DNA binding capacity of IRF3, thereby suppressing the transcription of IFN-β and downstream IFN-stimulated genes (ISGs). In addition, LYAR inhibits nuclear factor-κB (NF-κB)-mediated expression of proinflammatory cytokines. In summary, our study reveals the mechanism of LYAR in modulating IFN-β-mediated innate immune responses by targeting phosphorylated IRF3, which not only helps us to better understand the mechanisms of LYAR-regulated virus replication but also uncovers a novel role of LYAR in host innate immunity.
Identifiants
pubmed: 31413131
pii: JVI.00769-19
doi: 10.1128/JVI.00769-19
pmc: PMC6803289
pii:
doi:
Substances chimiques
DNA-Binding Proteins
0
IRF3 protein, human
0
Interferon Regulatory Factor-3
0
LYAR protein, human
0
Nuclear Proteins
0
Interferon-beta
77238-31-4
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
Copyright © 2019 American Society for Microbiology.
Références
Curr Opin Virol. 2011 Dec;1(6):519-25
pubmed: 22328912
Nat Rev Immunol. 2006 Sep;6(9):644-58
pubmed: 16932750
Cell Death Differ. 2017 Sep;24(9):1645-1654
pubmed: 28686580
Mol Cell Biol. 1998 Mar;18(3):1359-68
pubmed: 9488451
EMBO J. 1998 Feb 16;17(4):1087-95
pubmed: 9463386
J Virol. 2005 May;79(10):6410-8
pubmed: 15858024
Hepatology. 2014 Apr;59(4):1262-72
pubmed: 23929627
Proteome Sci. 2010 Jun 18;8:35
pubmed: 20565811
Microbes Infect. 2011 Apr;13(4):291-302
pubmed: 21256242
J Immunol. 2017 May 1;198(9):3690-3704
pubmed: 28356387
J Virol. 2015 Apr;89(7):3671-82
pubmed: 25589657
J Immunol. 2014 Oct 1;193(7):3436-45
pubmed: 25172485
J Virol. 2007 Jul;81(14):7749-58
pubmed: 17507495
Cell. 2005 Sep 9;122(5):669-82
pubmed: 16125763
Nat Immunol. 2006 Jun;7(6):598-605
pubmed: 16699525
Nat Rev Immunol. 2012 Jun 01;12(7):474
pubmed: 22653229
Genes Dev. 1993 May;7(5):735-48
pubmed: 8491376
MBio. 2018 Jan 30;9(1):
pubmed: 29382735
PLoS Pathog. 2015 Mar 11;11(3):e1004751
pubmed: 25760631
Annu Rev Immunol. 2009;27:693-733
pubmed: 19302050
Biochem Biophys Res Commun. 2001 May 25;283(5):1150-6
pubmed: 11355893
Cold Spring Harb Symp Quant Biol. 2013;78:105-16
pubmed: 24092468
Cell Host Microbe. 2017 Jul 12;22(1):86-98.e4
pubmed: 28704656
Genes Dev. 2016 May 1;30(9):1086-100
pubmed: 27125670
Immunity. 2010 Dec 14;33(6):863-77
pubmed: 21167755
J Virol. 2017 Jun 26;91(14):
pubmed: 28468885
J Leukoc Biol. 2017 Jul;102(1):163-170
pubmed: 28465448
Front Immunol. 2018 May 28;9:1135
pubmed: 29892288
Immunity. 2011 Sep 23;35(3):426-40
pubmed: 21903422
Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):2241-6
pubmed: 26858407
Nucleic Acids Res. 2014 Sep;42(15):9740-52
pubmed: 25092918
J Immunol. 2014 Oct 15;193(8):4125-36
pubmed: 25225669
Immunity. 2006 Sep;25(3):349-60
pubmed: 16979567
Immunity. 2019 Apr 16;50(4):907-923
pubmed: 30995506
Proc Natl Acad Sci U S A. 2013 Nov 26;110(48):19183-4
pubmed: 24225850
J Leukoc Biol. 2014 Dec;96(6):1055-63
pubmed: 25157027
Science. 2003 May 16;300(5622):1148-51
pubmed: 12702806
Antiviral Res. 2018 Aug;156:116-127
pubmed: 29906476
Virology. 2011 Mar 15;411(2):180-93
pubmed: 21211811
Nat Rev Immunol. 2005 May;5(5):375-86
pubmed: 15864272
J Virol. 2011 Sep;85(17):8460-6
pubmed: 21490091
PLoS Pathog. 2008 Nov;4(11):e1000196
pubmed: 18989459
PLoS One. 2015 Dec 02;10(12):e0143613
pubmed: 26629815
Cell Physiol Biochem. 2018;51(1):173-185
pubmed: 30439714
J Virol. 2017 Oct 13;91(21):
pubmed: 28794041
Oncotarget. 2015 Oct 20;6(32):32890-901
pubmed: 26413750
Virology. 1995 Jul 10;210(2):508-11
pubmed: 7618288
J Virol. 2018 Nov 12;92(23):
pubmed: 30209172
Mol Cell Biol. 1998 May;18(5):2986-96
pubmed: 9566918
Virus Res. 2015 Nov 2;209:11-22
pubmed: 25678267
Nat Rev Immunol. 2014 May;14(5):315-28
pubmed: 24762827
Sci Rep. 2017 Oct 17;7(1):13339
pubmed: 29042669
Nature. 2005 Oct 20;437(7062):1167-72
pubmed: 16177806
Mol Cell. 1998 Mar;1(4):507-18
pubmed: 9660935