The ETS transcription factor ELF1 regulates a broadly antiviral program distinct from the type I interferon response.
A549 Cells
Animals
Antiviral Agents
/ pharmacology
Female
Gene Expression Regulation
/ drug effects
Humans
Immunity, Innate
Influenza A virus
/ drug effects
Interferon Type I
/ pharmacology
Mice
Mice, Inbred C57BL
NF-kappa B
/ genetics
Nuclear Proteins
/ genetics
Orthomyxoviridae Infections
/ drug therapy
Phosphorylation
STAT1 Transcription Factor
Signal Transduction
Transcription Factors
/ genetics
Virus Replication
/ drug effects
Journal
PLoS pathogens
ISSN: 1553-7374
Titre abrégé: PLoS Pathog
Pays: United States
ID NLM: 101238921
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
07
02
2019
accepted:
11
10
2019
revised:
26
12
2019
pubmed:
5
11
2019
medline:
5
3
2020
entrez:
5
11
2019
Statut:
epublish
Résumé
Induction of vast transcriptional programs is a central event of innate host responses to viral infections. Here we report a transcriptional program with potent antiviral activity, driven by E74-like ETS transcription factor 1 (ELF1). Using microscopy to quantify viral infection over time, we found that ELF1 inhibits eight diverse RNA and DNA viruses after multi-cycle replication. Elf1 deficiency results in enhanced susceptibility to influenza A virus infections in mice. ELF1 does not feed-forward to induce interferons, and ELF1's antiviral effect is not abolished by the absence of STAT1 or by inhibition of JAK phosphorylation. Accordingly, comparative expression analyses by RNA-seq revealed that the ELF1 transcriptional program is distinct from interferon signatures. Thus, ELF1 provides an additional layer of the innate host response, independent from the action of type I interferons.
Identifiants
pubmed: 31682641
doi: 10.1371/journal.ppat.1007634
pii: PPATHOGENS-D-19-00251
pmc: PMC6932815
doi:
Substances chimiques
Antiviral Agents
0
ELF1 protein, human
0
Interferon Type I
0
NF-kappa B
0
Nuclear Proteins
0
STAT1 Transcription Factor
0
STAT1 protein, human
0
Transcription Factors
0
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
e1007634Subventions
Organisme : NIAID NIH HHS
ID : HHSN272201400008C
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI091707
Pays : United States
Organisme : NIAID NIH HHS
ID : R00 AI121473
Pays : United States
Organisme : NIAID NIH HHS
ID : K99 AI121473
Pays : United States
Organisme : NIAID NIH HHS
ID : T32 AI007180
Pays : United States
Organisme : NIAID NIH HHS
ID : U19 AI135972
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI143639
Pays : United States
Organisme : NIH HHS
ID : S10 OD018522
Pays : United States
Organisme : NIH HHS
ID : DP5 OD012142
Pays : United States
Déclaration de conflit d'intérêts
The authors have declared that no competing interests exist.
Références
Genome Biol. 2014 Feb 03;15(2):R29
pubmed: 24485249
J Virol. 2003 Sep;77(17):9192-203
pubmed: 12915535
Genes Dev. 1988 Apr;2(4):383-93
pubmed: 3371658
J Nephrol. 2013 Nov-Dec;26(6):953-9
pubmed: 23807646
Nature. 2011 Apr 28;472(7344):481-5
pubmed: 21478870
Lancet. 2018 Jun 16;391(10138):2395-2398
pubmed: 29916371
Nature. 2013 Jan 3;493(7430):51-5
pubmed: 23235831
Biochim Biophys Acta. 2013 Jan;1835(1):76-85
pubmed: 23147197
Proc Natl Acad Sci U S A. 1990 Nov;87(21):8555-9
pubmed: 2236065
Hepatology. 2014 Apr;59(4):1262-72
pubmed: 23929627
Bioinformatics. 2014 Apr 1;30(7):923-30
pubmed: 24227677
Proc Natl Acad Sci U S A. 2009 Jan 13;106(2):450-5
pubmed: 19129502
Nat Immunol. 2019 Feb;20(2):152-162
pubmed: 30643259
Nature. 2014 Jun 19;510(7505):363-9
pubmed: 24919153
J Immunol. 2018 Jan 1;200(1):209-217
pubmed: 29180486
Crit Rev Biochem Mol Biol. 2013 Nov-Dec;48(6):522-43
pubmed: 24066765
J Immunol. 2002 Nov 15;169(10):6048-55
pubmed: 12421992
EMBO J. 2013 Oct 16;32(20):2751-63
pubmed: 24065129
Biochem Soc Trans. 2009 Dec;37(Pt 6):1248-53
pubmed: 19909256
Immunity. 2014 Jun 19;40(6):880-95
pubmed: 24882218
Hum Mol Genet. 2011 Feb 1;20(3):601-7
pubmed: 21044949
J Virol. 2003 May;77(9):5295-304
pubmed: 12692231
Genome Biol. 2014;15(12):550
pubmed: 25516281
J Virol. 2005 Jan;79(2):1113-24
pubmed: 15613339
J Hum Genet. 2015 Sep;60(9):525-31
pubmed: 26084578
J Virol. 2017 Oct 27;91(22):null
pubmed: 28835505
Science. 1994 Jun 24;264(5167):1921-4
pubmed: 8009222
J Biol Chem. 2001 May 18;276(20):17181-9
pubmed: 11278640
Nucleic Acids Res. 2015 Apr 20;43(7):e47
pubmed: 25605792
Immunity. 2006 Sep;25(3):361-72
pubmed: 16979568
Genome Biol. 2010;11(2):R14
pubmed: 20132535
J Immunol. 2014 Jun 15;192(12):5459-68
pubmed: 24907379
Am J Physiol Lung Cell Mol Physiol. 2017 Jun 1;312(6):L1003-L1017
pubmed: 28385807
Immunity. 2011 May 27;34(5):629-36
pubmed: 21616433
FEBS Lett. 1997 May 12;408(1):47-51
pubmed: 9180266
J Immunol. 1998 Mar 15;160(6):2794-801
pubmed: 9510181
Cell. 2015 Feb 12;160(4):631-643
pubmed: 25679759
Cell. 1993 Oct 8;75(1):83-97
pubmed: 8402903
Gut. 2006 Aug;55(8):1071-3
pubmed: 16849343
Gastroenterology. 2013 Apr;144(4):781-8
pubmed: 23266558
Mol Cell Biol. 1996 Dec;16(12):6829-40
pubmed: 8943338
Sci Rep. 2015 Dec 08;5:17497
pubmed: 26643049
Lancet. 2017 Nov 4;390(10107):2099-2109
pubmed: 28647173
J Intern Med. 2008 Jun;263(6):591-6
pubmed: 18479258
IUBMB Life. 2010 Oct;62(10):724-31
pubmed: 20979208
Nat Immunol. 2013 Dec;14(12):1237-46
pubmed: 24185615
Nature. 2014 Jan 30;505(7485):691-5
pubmed: 24284630
Science. 2015 Apr 24;348(6233):448-53
pubmed: 25814066
Proc Natl Acad Sci U S A. 2008 May 13;105(19):7034-9
pubmed: 18467494
Cell. 1996 Feb 9;84(3):431-42
pubmed: 8608597
Science. 2005 Feb 4;307(5710):734-8
pubmed: 15692052
J Exp Med. 2016 Nov 14;213(12):2527-2538
pubmed: 27821552
J Innate Immun. 2017;9(2):145-161
pubmed: 27811478
Blood. 2011 Feb 10;117(6):1880-7
pubmed: 21148815
Annu Rev Virol. 2019 Sep 29;6(1):567-584
pubmed: 31283436
Mol Cell Biol. 1990 Jun;10(6):2448-57
pubmed: 2342456
JCI Insight. 2016 Aug 18;1(13):e87899
pubmed: 27668286
J Virol. 2002 May;76(9):4430-40
pubmed: 11932410
Immunity. 2013 May 23;38(5):918-29
pubmed: 23684984
J Gastroenterol. 2016 Jul;51(7):672-81
pubmed: 26511940
J Immunol. 2010 May 1;184(9):5179-85
pubmed: 20308629
PLoS Pathog. 2016 Dec 21;12(12):e1006102
pubmed: 28002492
Nat Methods. 2015 Apr;12(4):357-60
pubmed: 25751142
Biochimie. 2008 Jul;90(7):976-87
pubmed: 18226599
Genes Dev. 2007 Aug 1;21(15):1882-94
pubmed: 17652178
Am J Physiol. 1995 Mar;268(3 Pt 1):L347-60
pubmed: 7900815
Bioinformatics. 2015 Sep 1;31(17):2912-4
pubmed: 25964631
Cell Host Microbe. 2014 Jun 11;15(6):706-16
pubmed: 24922573
Am J Physiol Cell Physiol. 2016 Apr 15;310(8):C643-62
pubmed: 26825122
EMBO J. 1994 Jan 1;13(1):158-67
pubmed: 8306959
Immunity. 2000 Dec;13(6):795-804
pubmed: 11163195
Annu Rev Pathol. 2016 May 23;11:127-48
pubmed: 26907531
J Interferon Res. 1994 Oct;14(5):235-8
pubmed: 7861027
Annu Rev Immunol. 2014;32:513-45
pubmed: 24555472
J Virol. 1996 Jul;70(7):4805-10
pubmed: 8676512
Nature. 1998 Feb 12;391(6668):700-3
pubmed: 9490414
Genes Dev. 1989 Sep;3(9):1362-71
pubmed: 2606351
Nat Biotechnol. 2010 Feb;28(2):167-71
pubmed: 20118917