Virus-Mediated Suppression of the Antigen Presentation Molecule MR1.
Antigen Presentation
/ immunology
Cell Line
Cell Membrane
/ metabolism
Cytomegalovirus
/ physiology
Female
Fibroblasts
/ metabolism
Gene Expression Regulation, Viral
/ drug effects
Herpesvirus 1, Human
/ physiology
Histocompatibility Antigens Class I
/ metabolism
Humans
Jurkat Cells
Ligands
Male
Minor Histocompatibility Antigens
/ metabolism
Mucosal-Associated Invariant T Cells
/ immunology
Proteasome Inhibitors
/ pharmacology
Protein Serine-Threonine Kinases
/ metabolism
Proteolysis
/ drug effects
Viral Proteins
/ metabolism
MAIT cell
MR1
cytomegalovirus
herpes simplex virus
herpesvirus
immune evasion
virus targeting of MHC I-like molecules
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
03 03 2020
03 03 2020
Historique:
received:
26
09
2019
revised:
18
12
2019
accepted:
04
02
2020
entrez:
5
3
2020
pubmed:
5
3
2020
medline:
25
3
2021
Statut:
ppublish
Résumé
The antigen-presenting molecule MR1 presents microbial metabolites related to vitamin B2 biosynthesis to mucosal-associated invariant T cells (MAIT cells). Although bacteria and fungi drive the MR1 biosynthesis pathway, viruses have not previously been implicated in MR1 expression or its antigen presentation. We demonstrate that several herpesviruses inhibit MR1 cell surface upregulation, including a potent inhibition by herpes simplex virus type 1 (HSV-1). This virus profoundly suppresses MR1 cell surface expression and targets the molecule for proteasomal degradation, whereas ligand-induced cell surface expression of MR1 prior to infection enables MR1 to escape HSV-1-dependent targeting. HSV-1 downregulation of MR1 is dependent on de novo viral gene expression, and we identify the Us3 viral gene product as functioning to target MR1. Furthermore, HSV-1 downregulation of MR1 disrupts MAIT T cell receptor (TCR) activation. Accordingly, virus-mediated targeting of MR1 defines an immunomodulatory strategy that functionally disrupts the MR1-MAIT TCR axis.
Identifiants
pubmed: 32130899
pii: S2211-1247(20)30171-6
doi: 10.1016/j.celrep.2020.02.017
pmc: PMC7798347
mid: NIHMS1660175
pii:
doi:
Substances chimiques
Histocompatibility Antigens Class I
0
Ligands
0
MR1 protein, human
0
Minor Histocompatibility Antigens
0
Proteasome Inhibitors
0
Viral Proteins
0
Protein Serine-Threonine Kinases
EC 2.7.11.1
US3 protein, Human herpesvirus 1
EC 2.7.11.1
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
2948-2962.e4Subventions
Organisme : NEI NIH HHS
ID : P30 EY008098
Pays : United States
Organisme : NIAID NIH HHS
ID : R01 AI122640
Pays : United States
Organisme : NEI NIH HHS
ID : R01 EY015291
Pays : United States
Informations de copyright
Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests The authors declare no competing interests.
Références
J Virol. 2011 Aug;85(16):8093-104
pubmed: 21653669
J Exp Med. 2017 Jan;214(1):73-89
pubmed: 28011863
J Virol. 2011 Aug;85(15):7644-57
pubmed: 21632771
Blood. 2013 Feb 14;121(7):1124-35
pubmed: 23243281
Nat Commun. 2013;4:2142
pubmed: 23846752
Proc Natl Acad Sci U S A. 2016 Sep 6;113(36):10133-8
pubmed: 27543331
J Gen Virol. 2017 Jul;98(7):1795-1805
pubmed: 28745271
PLoS Pathog. 2014 May 01;10(5):e1004058
pubmed: 24787765
PLoS One. 2012;7(6):e39875
pubmed: 22768151
PLoS One. 2014 Nov 04;9(11):e111323
pubmed: 25369333
Biochem Biophys Res Commun. 1997 Sep 29;238(3):697-702
pubmed: 9325151
Nat Immunol. 2016 May;17(5):531-7
pubmed: 27043408
Nat Rev Microbiol. 2018 Mar;16(3):143-155
pubmed: 29332945
J Exp Med. 2012 Apr 9;209(4):761-74
pubmed: 22412157
J Exp Med. 2008 May 12;205(5):1201-11
pubmed: 18443227
EMBO Mol Med. 2018 Feb;10(2):188-199
pubmed: 29282224
J Virol. 2008 May;82(9):4585-94
pubmed: 18287244
Nat Immunol. 2010 Aug;11(8):701-8
pubmed: 20581831
Nat Immunol. 2006 Aug;7(8):835-42
pubmed: 16845396
PLoS Negl Trop Dis. 2018 Jan 22;12(1):e0006154
pubmed: 29357366
J Virol. 2004 Feb;78(4):1763-74
pubmed: 14747541
PLoS One. 2017 Apr 6;12(4):e0175345
pubmed: 28384290
Science. 1995 Aug 4;269(5224):693-5
pubmed: 7624800
Sci Rep. 2016 Feb 03;6:20358
pubmed: 26837580
Nat Immunol. 2018 Mar;19(3):302-314
pubmed: 29476184
Immunity. 2016 Jan 19;44(1):32-45
pubmed: 26795251
J Allergy Clin Immunol. 2013 Jun;131(6):1594-603
pubmed: 23522482
Immunol Cell Biol. 2018 Jul;96(6):598-606
pubmed: 29569752
J Clin Invest. 2010 Sep;120(9):3191-208
pubmed: 20679731
Science. 2016 Jan 15;351(6270):
pubmed: 26816384
PLoS Pathog. 2013;9(10):e1003681
pubmed: 24130485
N Engl J Med. 2018 Aug 9;379(6):557-566
pubmed: 30089069
Nature. 2014 Jun 12;510(7504):288-92
pubmed: 24870241
Proc Natl Acad Sci U S A. 2017 Jul 3;114(27):E5434-E5443
pubmed: 28630305
Cell. 1985 Jul;41(3):987-97
pubmed: 3924414
PLoS One. 2013 Aug 12;8(8):e72050
pubmed: 23951282
Nat Commun. 2018 Nov 9;9(1):4706
pubmed: 30413689
Nat Immunol. 2017 Apr;18(4):402-411
pubmed: 28166217
Sci Immunol. 2018 Jul 13;3(25):
pubmed: 30006464
Elife. 2017 May 18;6:
pubmed: 28518056
Blood. 2013 Feb 7;121(6):951-61
pubmed: 23255555
Nature. 1995 Jun 1;375(6530):415-8
pubmed: 7760936
Blood. 2013 Jan 24;121(4):614-23
pubmed: 23223428
Eur J Clin Invest. 2016 Feb;46(2):170-80
pubmed: 26681320
J Exp Med. 2014 Jul 28;211(8):1585-600
pubmed: 25049336
Cells. 2014 May 20;3(2):438-54
pubmed: 24852129
Nature. 2012 Nov 29;491(7426):717-23
pubmed: 23051753
Nat Commun. 2016 Jun 23;7:11653
pubmed: 27337592
J Gen Virol. 1990 Dec;71 ( Pt 12):2961-7
pubmed: 2177088
Semin Immunol. 2015 Mar;27(2):125-37
pubmed: 25887630
Cell. 1994 May 20;77(4):525-35
pubmed: 8187174
Nature. 2003 Mar 13;422(6928):164-9
pubmed: 12634786
Immunol Cell Biol. 2015 Feb;93(2):177-88
pubmed: 25348935
Proc Natl Acad Sci U S A. 1987 Mar;84(5):1356-60
pubmed: 2950523
Proc Natl Acad Sci U S A. 1987 Apr;84(7):1926-30
pubmed: 3031658
J Allergy Clin Immunol. 2012 Sep;130(3):683-691.e2
pubmed: 22840852
Nat Protoc. 2006;1(1):406-17
pubmed: 17406263
PLoS Biol. 2010 Jun 29;8(6):e1000407
pubmed: 20613858
Curr Microbiol. 2016 May;72(5):529-37
pubmed: 26758707
Nat Commun. 2017 Mar 08;8:14599
pubmed: 28272391
Eur J Immunol. 2016 Sep;46(9):2099-102
pubmed: 27479232
J Virol. 2008 Apr;82(7):3381-90
pubmed: 18234803
J Virol. 2016 Apr 14;90(9):4520-4529
pubmed: 26912615
PLoS Pathog. 2015 Aug 21;11(8):e1005072
pubmed: 26295709
Adv Exp Med Biol. 2018;1045:45-62
pubmed: 29896662
Front Immunol. 2017 Apr 11;8:390
pubmed: 28443092
J Virol. 1996 Dec;70(12):8833-49
pubmed: 8971012
J Virol. 2015 Jul;89(13):6646-55
pubmed: 25878107
Nucleic Acids Res. 1986 Feb 25;14(4):1765-77
pubmed: 3005981
Eur J Immunol. 2016 Sep;46(9):2204-10
pubmed: 27296288
Front Immunol. 2015 Jun 16;6:303
pubmed: 26136743
Nature. 2014 May 15;509(7500):361-5
pubmed: 24695216
J Immunol. 2003 Dec 15;171(12):6733-41
pubmed: 14662877
Front Immunol. 2018 Jun 04;9:1103
pubmed: 29942301
Curr Opin Immunol. 2016 Jun;40:43-50
pubmed: 27065088