A CRISPR Activation Screen Identifies Genes That Protect against Zika Virus Infection.
Alternative Splicing
Clustered Regularly Interspaced Short Palindromic Repeats
Disease Resistance
/ genetics
Gene Expression
Genetic Testing
/ methods
Host-Pathogen Interactions
/ genetics
Humans
Interleukins
/ genetics
Nuclear Proteins
/ genetics
Phosphoproteins
/ genetics
Protein Transport
Reproducibility of Results
Virus Activation
Virus Replication
Zika Virus
/ physiology
Zika Virus Infection
/ genetics
CRISPR activation
Zika virus
genome-wide screen
interferon-stimulated genes
interferons
Journal
Journal of virology
ISSN: 1098-5514
Titre abrégé: J Virol
Pays: United States
ID NLM: 0113724
Informations de publication
Date de publication:
15 08 2019
15 08 2019
Historique:
received:
07
02
2019
accepted:
22
05
2019
pubmed:
31
5
2019
medline:
4
6
2020
entrez:
31
5
2019
Statut:
epublish
Résumé
Zika virus (ZIKV) is an arthropod-borne emerging pathogen causing febrile illness. ZIKV is associated Guillain-Barré syndrome and other neurological complications. Infection during pregnancy is associated with pregnancy complications and developmental and neurological abnormalities collectively defined as congenital Zika syndrome. There is still no vaccine or specific treatment for ZIKV infection. To identify host factors that can rescue cells from ZIKV infection, we used a genome-scale CRISPR activation screen. Our highly ranking hits included a short list of interferon-stimulated genes (ISGs) previously reported to have antiviral activity. Validation of the screen results highlighted interferon lambda 2 (IFN-λ2) and interferon alpha-inducible protein 6 (IFI6) as genes providing high levels of protection from ZIKV. Activation of these genes had an effect on an early stage in viral infection. In addition, infected cells expressing single guide RNAs (sgRNAs) for both of these genes displayed lower levels of cell death than did the controls. Furthermore, the identified genes were significantly induced in ZIKV-infected placenta explants. Thus, these results highlight a set of ISGs directly relevant for rescuing cells from ZIKV infection or its associated cell death and substantiate CRISPR activation screens as a tool to identify host factors impeding pathogen infection.
Identifiants
pubmed: 31142663
pii: JVI.00211-19
doi: 10.1128/JVI.00211-19
pmc: PMC6675891
pii:
doi:
Substances chimiques
IFNL4 protein, human
0
Interleukins
0
Nuclear Proteins
0
Phosphoproteins
0
IFI16 protein, human
148998-64-5
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NIAID NIH HHS
ID : R01 AI140718
Pays : United States
Informations de copyright
Copyright © 2019 American Society for Microbiology.
Références
Biochim Biophys Acta. 2003 Jul 30;1638(3):227-34
pubmed: 12878323
Trans R Soc Trop Med Hyg. 1954 Mar;48(2):139-45
pubmed: 13157159
BMC Genomics. 2004 Jan 19;5(1):8
pubmed: 14728724
Virology. 2004 Nov 10;329(1):119-33
pubmed: 15476880
Nat Struct Mol Biol. 2004 Nov;11(11):1060-7
pubmed: 15502848
Cancer Immunol Immunother. 2005 Aug;54(8):729-40
pubmed: 15685448
J Virol. 2006 Mar;80(6):2976-86
pubmed: 16501107
J Clin Invest. 2007 Oct;117(10):3107-17
pubmed: 17823654
J Biol Chem. 2007 Dec 14;282(50):36354-61
pubmed: 17901050
Virology. 2008 Sep 30;379(2):314-23
pubmed: 18676000
Proc Natl Acad Sci U S A. 2008 Dec 23;105(51):20380-5
pubmed: 19091943
J Virol. 2010 Apr;84(7):3220-9
pubmed: 20071582
Semin Cell Dev Biol. 2010 Jul;21(5):479-85
pubmed: 20223290
J Immunol. 2010 May 15;184(10):5768-76
pubmed: 20382888
J Virol. 2010 Aug;84(16):8332-41
pubmed: 20534863
Nature. 2011 Apr 28;472(7344):481-5
pubmed: 21478870
Nat Methods. 2012 Jun 28;9(7):676-82
pubmed: 22743772
Nat Methods. 2012 Jul;9(7):671-5
pubmed: 22930834
J Virol. 2013 Apr;87(7):4080-5
pubmed: 23325687
Nat Methods. 2013 Oct;10(10):973-6
pubmed: 23892895
Nat Methods. 2013 Oct;10(10):977-9
pubmed: 23892898
Nat Biotechnol. 2013 Sep;31(9):833-8
pubmed: 23907171
Hepatology. 2014 Apr;59(4):1262-72
pubmed: 23929627
Annu Rev Immunol. 2014;32:513-45
pubmed: 24555472
Mol Cell Biochem. 2014 Dec;397(1-2):157-65
pubmed: 25138703
Cell. 2014 Oct 23;159(3):647-61
pubmed: 25307932
Cell. 2014 Oct 23;159(3):635-46
pubmed: 25307933
Genome Biol. 2014;15(12):554
pubmed: 25476604
Nature. 2015 Jan 29;517(7536):583-8
pubmed: 25494202
Viruses. 2015 Jan 06;7(1):37-51
pubmed: 25569078
Nat Methods. 2015 Apr;12(4):326-8
pubmed: 25730490
Cell Rep. 2015 Jul 28;12(4):673-83
pubmed: 26190106
PLoS One. 2015 Aug 05;10(8):e0132743
pubmed: 26244642
PLoS Negl Trop Dis. 2016 May 05;10(5):e0004658
pubmed: 27149521
PLoS Negl Trop Dis. 2016 May 10;10(5):e0004695
pubmed: 27163257
J Virol. 2016 Jul 11;90(15):6832-45
pubmed: 27194766
Nat Methods. 2016 Jul;13(7):563-567
pubmed: 27214048
Cell Rep. 2016 Jun 28;16(1):232-246
pubmed: 27342126
Nature. 2016 Jul 7;535(7610):159-63
pubmed: 27383987
Nature. 2016 Jul 7;535(7610):164-8
pubmed: 27383988
Emerg Microbes Infect. 2016 Aug 24;5:e93
pubmed: 27553173
Nat Rev Microbiol. 2016 Nov;14(11):707-715
pubmed: 27573577
Elife. 2016 Sep 08;5:null
pubmed: 27608486
Biol Cell. 2017 Feb;109(2):94-112
pubmed: 27673746
Front Microbiol. 2017 Feb 20;8:240
pubmed: 28265266
Nat Protoc. 2017 Apr;12(4):828-863
pubmed: 28333914
Lancet. 2017 Aug 26;390(10097):861-870
pubmed: 28647172
Cell Rep. 2017 Aug 15;20(7):1503-1512
pubmed: 28813663
Sci Rep. 2017 Sep 12;7(1):11393
pubmed: 28900143
Cell Host Microbe. 2017 Sep 13;22(3):366-376.e3
pubmed: 28910635
J Virol. 2017 Nov 30;91(24):
pubmed: 29021400
Cell Rep. 2017 Nov 7;21(6):1588-1599
pubmed: 29117563
Cell Rep. 2017 Nov 7;21(6):1600-1612
pubmed: 29117564
Nat Rev Microbiol. 2018 Feb 12;16(3):125-142
pubmed: 29430005
Nat Microbiol. 2018 Nov;3(11):1214-1223
pubmed: 30224801
J Virol. 2018 Dec 10;93(1):
pubmed: 30305350