Cell Reports
Volume 30, Issue 9, 3 March 2020, Pages 2948-2962.e4
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Article
Virus-Mediated Suppression of the Antigen Presentation Molecule MR1

https://doi.org/10.1016/j.celrep.2020.02.017Get rights and content
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Highlights

  • The herpesviruses HSV-1 and CMV suppress the antigen presentation molecule MR1

  • HSV-1 targets immature MR1 for degradation although mature MR1 remains protected

  • The Us3 protein of HSV-1 is partially responsible for suppression of MR1

  • Suppression of MR1 by HSV-1 inhibits MAIT TCR-dependent activation

Summary

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.

Keywords

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

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These authors contributed equally

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