Virus-Mediated Suppression of the Antigen Presentation Molecule MR1

BP McSharry; C Samer; HEG McWilliam; CL Ashley; MB Yee; M Steain; L Liu; DP Fairlie; PR Kinchington; J McCluskey; A Abendroth; JA Villadangos; J Rossjohn; B Slobedman

Journal article

Virus-Mediated Suppression of the Antigen Presentation Molecule MR1

BP McSharry, C Samer, HEG McWilliam, CL Ashley, MB Yee, M Steain, L Liu, DP Fairlie, PR Kinchington, J McCluskey, A Abendroth, JA Villadangos, J Rossjohn, B Slobedman

Cell Reports | CELL PRESS | Published : 2020

DOI: 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. H..

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University of Melbourne Researchers

Hamish McWilliam Author

James McCluskey Author

Jose Villadangos Author

Jamie Rossjohn Author

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Grants

Awarded by Research to Prevent Blindness

Funding Acknowledgements

We wish to thank Prof. Roger Everett for providing the HSV-1 ICP0 and VHS mutant viruses, Prof. William Rawlinson for the MCMV Smith strain, Dr. Richard Stanton for the bacterial artificial chromosome (BAC)-derived HCMV Merlin strain, and Dr. Russell Diefenbach for HSV-1 strain F. C.S. is supported by an Australian Postgraduate Award. J.R. is supported by an Australian Research Council (ARC) Australian Laureate Fellowship. D.P.F. is supported by a National Health and Medical Research Council of Australia Senior Principal Research Fellowship (1117017) and an ARC Centre of Excellence grant (CE140100011). P.R.K. was supported by awards from the National Institutes of Health USA (R01-EY015291 and R01-AI122640), NEI CORE grant for Vision Research P30-EY08098, and Unrestricted awards from the Research to Prevent Blindness Inc. and The Eye & Ear Foundation of Pittsburgh. H.E.G.M. is supported by an ARC Discovery Early Career Researcher Award (DE170100575). J.A.V. is supported by a National Health and Medical Research Council of Australia Principal Research Fellowship (1154502) and a Program Grant (1113293) and by an ARC Discovery Project Grant 170102471).