Virus-Mediated Suppression of the Antigen Presentation Molecule MR1

Brian P. McSharry, Carolyn Samer, Hamish E.G. McWilliam, Caroline L. Ashley, Michael B. Yee, Megan Steain, Ligong Liu, David P. Fairlie, Paul R. Kinchington, James McCluskey, Allison Abendroth, Jose A. Villadangos, Jamie Rossjohn, Barry Slobedman

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11 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)2948-2962
Number of pages15
JournalCell Reports
Volume30
Issue number9
DOIs
Publication statusPublished - 3 Mar 2020

Keywords

  • cytomegalovirus
  • herpes simplex virus
  • herpesvirus
  • immune evasion
  • MAIT cell
  • MR1
  • virus targeting of MHC I-like molecules

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