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Virus-mediated suppression of the antigen presentation Molecule MR1

McSharry, Brian P., Samer, Carolyn, McWilliam, Hamish E.G., Ashley, Caroline L., Yee, Michael B., Steain, Megan, Liu, Ligong, Fairlie, David P., Kinchington, Paul R., McCluskey, James, Abendroth, Allison, Villadangos, Jose A., Rossjohn, Jamie and Slobedman, Barry 2020. Virus-mediated suppression of the antigen presentation Molecule MR1. Cell Reports 30 (9) , 2948-2962e4. 10.1016/j.celrep.2020.02.017

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Abstract

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.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Medicine
Publisher: Elsevier
ISSN: 2211-1247
Date of First Compliant Deposit: 11 March 2020
Date of Acceptance: 4 February 2020
Last Modified: 12 Mar 2020 11:50
URI: http://orca.cf.ac.uk/id/eprint/130333

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