Necroptosis-based CRISPR knockout screen reveals Neuropilin-1 as a critical host factor for early stages of murine cytomegalovirus infection.
CRISPR
cytomegolovirus
necroptosis
neuropilin
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
18 08 2020
18 08 2020
Historique:
pubmed:
5
8
2020
medline:
7
10
2020
entrez:
5
8
2020
Statut:
ppublish
Résumé
Herpesviruses are ubiquitous human pathogens that cause a wide range of health complications. Currently, there is an incomplete understanding of cellular factors that contribute to herpesvirus infection. Here, we report an antiviral necroptosis-based genetic screen to identify novel host cell factors required for infection with the β-herpesvirus murine cytomegalovirus (MCMV). Our genome-wide CRISPR-based screen harnessed the capacity of herpesvirus mutants that trigger antiviral necroptotic cell death upon early viral gene expression. Vascular endothelial growth factor (VEGF) and semaphorin-binding receptor Neuropilin-1 (Nrp-1) emerge as crucial determinants of MCMV infection. We find that elimination of Nrp-1 impairs early viral gene expression and reduces infection rates in endothelial cells, fibroblasts, and macrophages. Furthermore, preincubation of virus with soluble Nrp-1 dramatically inhibits infection by reducing virus attachment. Thus, Nrp-1 is a key determinant of the initial phase of MCMV infection.
Identifiants
pubmed: 32747526
pii: 1921315117
doi: 10.1073/pnas.1921315117
pmc: PMC7443917
doi:
Substances chimiques
Neuropilin-1
144713-63-3
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
20109-20116Subventions
Organisme : NIDCR NIH HHS
ID : T32 DE014318
Pays : United States
Organisme : NIH HHS
ID : DP5 OD012198
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI141970
Pays : United States
Organisme : NIDCR NIH HHS
ID : F31 DE029395
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI020211
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001120
Pays : United States
Déclaration de conflit d'intérêts
The authors declare no competing interest.
Références
Cell Host Microbe. 2015 Feb 11;17(2):243-51
pubmed: 25674983
Mol Cell. 2014 Apr 24;54(2):273-80
pubmed: 24766891
Viruses. 2017 Sep 02;9(9):
pubmed: 28869497
J Biol Chem. 2015 Dec 4;290(49):29120-6
pubmed: 26451046
Proc Natl Acad Sci U S A. 2019 Apr 2;116(14):7043-7052
pubmed: 30894498
Nat Commun. 2015 Feb 11;6:6240
pubmed: 25670642
Virol J. 2016 May 06;13:77
pubmed: 27154074
Cell Host Microbe. 2010 Apr 22;7(4):302-13
pubmed: 20413098
Proc Natl Acad Sci U S A. 2007 Apr 10;104(15):6152-7
pubmed: 17405859
Nat Microbiol. 2016 Jun 06;1(8):16082
pubmed: 27573107
Genome Biol. 2014;15(12):554
pubmed: 25476604
Nat Genet. 2017 Feb;49(2):193-203
pubmed: 27992415
mBio. 2017 Jan 17;8(1):
pubmed: 28096485
Nat Rev Microbiol. 2017 Jun;15(6):351-364
pubmed: 28420884
Curr Opin Virol. 2013 Jun;3(3):296-306
pubmed: 23773332
Mol Cell. 2014 Apr 10;54(1):133-146
pubmed: 24703947
Immunol Cell Biol. 1995 Aug;73(4):308-15
pubmed: 7493766
J Virol. 2006 Jan;80(2):710-22
pubmed: 16378974
FASEB J. 2006 Jul;20(9):1513-5
pubmed: 16754745
Nat Microbiol. 2018 Nov;3(11):1214-1223
pubmed: 30224801
Nature. 2007 Jul 26;448(7152):501-5
pubmed: 17618271
EMBO Rep. 2017 Aug;18(8):1429-1441
pubmed: 28607035
Biochimie. 2001 Aug;83(8):811-7
pubmed: 11530214
Cell Death Differ. 2001 Feb;8(2):113-26
pubmed: 11313713
Proc Natl Acad Sci U S A. 2018 Oct 16;115(42):E9889-E9898
pubmed: 30275317
J Virol. 1999 Aug;73(8):6800-9
pubmed: 10400778
Mucosal Immunol. 2015 Jan;8(1):57-67
pubmed: 24894498
mBio. 2018 May 8;9(3):
pubmed: 29739904
J Virol. 2011 Oct;85(19):10346-53
pubmed: 21813614
Nat Protoc. 2017 Apr;12(4):828-863
pubmed: 28333914
Cell. 2018 Aug 23;174(5):1158-1171.e19
pubmed: 30057110
Cell Rep. 2015 Jul 28;12(4):673-83
pubmed: 26190106
Nat Commun. 2019 Jun 20;10(1):2699
pubmed: 31221976
Cell Death Differ. 2019 Jan;26(1):4-13
pubmed: 30050058
Nat Methods. 2014 Aug;11(8):783-784
pubmed: 25075903
Cell. 1996 Nov 1;87(3):427-36
pubmed: 8898196
Cell Host Microbe. 2012 Mar 15;11(3):290-7
pubmed: 22423968
Med Microbiol Immunol. 2015 Jun;204(3):273-84
pubmed: 25894764
Proc Natl Acad Sci U S A. 2014 Oct 28;111(43):15438-43
pubmed: 25316792
Cell Death Dis. 2018 Jul 26;9(8):816
pubmed: 30050136
Cell Rep. 2016 Jun 28;16(1):232-246
pubmed: 27342126
J Biol Chem. 2012 Mar 30;287(14):11082-9
pubmed: 22318724
Cell Host Microbe. 2014 Mar 12;15(3):351-62
pubmed: 24629341
Cell Host Microbe. 2015 Feb 11;17(2):229-42
pubmed: 25674982
FEMS Microbiol Rev. 1999 Jul;23(4):457-82
pubmed: 10422262
Sci Rep. 2015 Mar 09;5:8865
pubmed: 25746010
Curr Opin Virol. 2018 Apr;29:87-100
pubmed: 29684735
PLoS Pathog. 2013;9(7):e1003493
pubmed: 23935483
Nat Rev Immunol. 2011 Dec 23;12(2):79-88
pubmed: 22193709
J Virol. 2015 Nov 18;90(3):1414-23
pubmed: 26581979
Virology. 1992 Nov;191(1):387-95
pubmed: 1329327
PLoS Pathog. 2017 Apr 12;13(4):e1006281
pubmed: 28403202
Cell Rep. 2017 Aug 15;20(7):1503-1512
pubmed: 28813663
J Virol. 2006 Jul;80(14):6844-54
pubmed: 16809290
PLoS One. 2012;7(11):e49177
pubmed: 23145112
Curr Opin Virol. 2012 Feb;2(1):37-42
pubmed: 22440964