Virus-Mediated Suppression of the Antigen Presentation Molecule MR1

• DOI: 10.1016/j.celrep.2020.02.017
• Publication Date: 2020-03-03T16:52:49Z
• Authors: Brian P. McSharry; Carolyn Samer; Hamish E.G. McWil...; 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
• Keywords: Presentation (obstetrics)

The antigen-presenting molecule MR1 presents microbial metabolites related to vitamin B2 biosynthesis mucosal-associated invariant T cells (MAIT cells). Although bacteria and fungi drive the pathway, viruses have not previously been implicated in expression or its antigen presentation. We demonstrate that several herpesviruses inhibit cell surface upregulation, including a potent inhibition by herpes simplex virus type 1 (HSV-1). This profoundly suppresses targets for proteasomal degradation, whereas ligand-induced of prior infection enables escape HSV-1-dependent targeting. HSV-1 downregulation is dependent on de novo viral gene expression, we identify Us3 product as functioning target MR1. Furthermore, disrupts MAIT receptor (TCR) activation. Accordingly, virus-mediated targeting defines an immunomodulatory strategy functionally MR1-MAIT TCR axis.