Virus-Mediated Suppression of the Antigen Presentation Molecule MR1.

Cell Reports
Brian P McSharryBarry Slobedman

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.

Citations

Sep 10, 2020·Frontiers in Immunology·Melina IoannidisMariolina Salio
Jul 25, 2020·Mucosal Immunology·Qiaochu LinThierry Mallevaey
Sep 24, 2020·Scientific Reports·Gitanjali A NarayananDavid M Lewinsohn
Aug 28, 2020·Frontiers in Immunology·Roman A Akasov, Evgeny V Khaydukov
Oct 23, 2020·Immunological Reviews·Hannah KaminskiLionel Couzi
Mar 24, 2021·Mucosal Immunology·Isabelle NelAgnès Lehuen
Oct 15, 2020·Immunity·François LegouxOlivier Lantz

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Methods Mentioned

BETA
flow cytometry
transfection
transgenic
PCR

Software Mentioned

FlowJo
GraphPad Prism

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