Identification of the Cell-Surface Protease ADAM9 as an Entry Factor for Encephalomyocarditis Virus.
ADAM Proteins
/ antagonists & inhibitors
Animals
Cardiovirus Infections
/ metabolism
Cell Line, Tumor
Cell Membrane
/ metabolism
Encephalomyocarditis virus
/ metabolism
Gene Knockout Techniques
Genome, Human
/ genetics
Humans
Membrane Proteins
/ antagonists & inhibitors
Mice
Virus Attachment
Virus Internalization
Virus Replication
disintegrin and metalloproteinase domain-containing protein 9 (ADAM9)
encephalomyocarditis virus
haploid genetic screen
Journal
mBio
ISSN: 2150-7511
Titre abrégé: mBio
Pays: United States
ID NLM: 101519231
Informations de publication
Date de publication:
13 08 2019
13 08 2019
Historique:
entrez:
15
8
2019
pubmed:
15
8
2019
medline:
6
5
2020
Statut:
epublish
Résumé
Encephalomyocarditis virus (EMCV) is an animal pathogen and an important model organism, whose receptor requirements are poorly understood. Here, we employed a genome-wide haploid genetic screen to identify novel EMCV host factors. In addition to the previously described picornavirus receptors sialic acid and glycosaminoglycans, this screen unveiled important new host factors for EMCV. These factors include components of the fibroblast growth factor (FGF) signaling pathway, such as the potential receptors FGFR1 and ADAM9, a cell-surface metalloproteinase. By employing various knockout cells, we confirmed the importance of the identified host factors for EMCV infection. The largest reduction in infection efficiency was observed in cells lacking ADAM9. Pharmacological inhibition of the metalloproteinase activity of ADAM9 did not affect virus infection. Moreover, reconstitution of inactive ADAM9 in knockout cells restored susceptibility to EMCV, pointing to a proteinase-independent role of ADAM9 in mediating EMCV infection. Using neutralization assays with ADAM9-specific antiserum and soluble receptor proteins, we provided evidence for a role of ADAM9 in EMCV entry. Finally, binding assays showed that ADAM9 facilitates attachment of EMCV to the cell surface. Together, our findings reveal a role for ADAM9 as a novel receptor or cofactor for EMCV.
Identifiants
pubmed: 31409686
pii: mBio.01780-19
doi: 10.1128/mBio.01780-19
pmc: PMC6692517
pii:
doi:
Substances chimiques
Membrane Proteins
0
ADAM Proteins
EC 3.4.24.-
ADAM9 protein, human
EC 3.4.24.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Wellcome Trust
Pays : United Kingdom
Informations de copyright
Copyright © 2019 Baggen et al.
Références
Sci Rep. 2017 Nov 8;7(1):15108
pubmed: 29118335
Nat Rev Mol Cell Biol. 2013 Mar;14(3):166-80
pubmed: 23403721
Nature. 2011 Aug 24;477(7364):340-3
pubmed: 21866103
Mol Cell Biol. 2009 May;29(10):2694-703
pubmed: 19273593
Eur J Cell Biol. 2012 Jun-Jul;91(6-7):472-85
pubmed: 22138087
Virol J. 2009 Sep 15;6:141
pubmed: 19751532
Vet Res. 2006 Nov-Dec;37(6):757-66
pubmed: 16973116
Biochem J. 2017 Apr 13;474(9):1467-1479
pubmed: 28264989
Science. 2014 Jun 27;344(6191):1506-10
pubmed: 24970085
Epidemiol Infect. 2005 Jun;133(3):547-57
pubmed: 15962562
Science. 1945 Jul 13;102(2637):31-3
pubmed: 17787415
J Virol. 2013 Jan;87(1):611-20
pubmed: 23097443
Cell Microbiol. 2015 Aug;17(8):1144-56
pubmed: 25645595
Cancer Res. 2005 Oct 15;65(20):9312-9
pubmed: 16230393
Emerg Infect Dis. 2009 Apr;15(4):640-6
pubmed: 19331761
J Virol. 1994 Nov;68(11):7308-19
pubmed: 7933115
mBio. 2019 Feb 5;10(1):
pubmed: 30723129
Science. 2017 May 26;356(6340):
pubmed: 28495876
Tumour Biol. 2017 Jul;39(7):1010428317716077
pubmed: 28675123
Nature. 2017 Jan 19;541(7637):412-416
pubmed: 28077878
Vector Borne Zoonotic Dis. 2011 Apr;11(4):367-74
pubmed: 21395427
Arch Virol. 2012 Jan;157(1):43-52
pubmed: 21989795
Nat Biotechnol. 2011 May 29;29(6):542-6
pubmed: 21623355
Nature. 2017 Oct 5;550(7674):114-118
pubmed: 28953874
Virulence. 2012 Jul 1;3(4):351-67
pubmed: 22722247
Proc Natl Acad Sci U S A. 2006 Aug 15;103(33):12417-22
pubmed: 16888036
Cancer Res. 2010 Oct 15;70(20):8187-98
pubmed: 20736367
J Virol. 2000 Feb;74(3):1477-85
pubmed: 10627559
PLoS Pathog. 2015 Mar 23;11(3):e1004733
pubmed: 25799064
J Virol. 2004 Aug;78(16):8909-16
pubmed: 15280499
Wien Klin Wochenschr. 2003;115 Suppl 3:61-7
pubmed: 15508783
Cell Rep. 2012 Nov 29;2(5):1187-96
pubmed: 23142662
J Cell Biol. 2013 Feb 18;200(4):493-504
pubmed: 23420874
Endocr Relat Cancer. 2012 Jun 18;19(4):R115-29
pubmed: 22508544
Nat Rev Mol Cell Biol. 2005 Jan;6(1):32-43
pubmed: 15688065
J Biol Chem. 1999 Feb 5;274(6):3531-40
pubmed: 9920899
EMBO J. 2007 Sep 5;26(17):4016-28
pubmed: 17717529
Intervirology. 2009;52(4):201-12
pubmed: 19556802
J Virol. 1994 Jun;68(6):3453-8
pubmed: 7514674
Proc Natl Acad Sci U S A. 2018 Jan 9;115(2):397-402
pubmed: 29284752
J Virol. 2009 Nov;83(22):11940-9
pubmed: 19740986
Biochem J. 2005 Jan 15;385(Pt 2):461-8
pubmed: 15361064
J Cell Sci. 2000 Jun;113 ( Pt 12):2319-28
pubmed: 10825303
Mol Cell Biol. 2002 Mar;22(5):1537-44
pubmed: 11839819