Varicella Zoster Virus Impairs Expression of the Nonclassical Major Histocompatibility Complex Class I-Related Gene Protein (MR1)

Shivam K Purohit; Carolyn Samer; Hamish EG McWilliam; Renee Traves; Megan Steain; Brian P McSharry; Paul R Kinchington; David C Tscharke; Jose A Villadangos; Jamie Rossjohn; Allison Abendroth; Barry Slobedman

Journal article

Varicella Zoster Virus Impairs Expression of the Nonclassical Major Histocompatibility Complex Class I-Related Gene Protein (MR1)

Shivam K Purohit, Carolyn Samer, Hamish EG McWilliam, Renee Traves, Megan Steain, Brian P McSharry, Paul R Kinchington, David C Tscharke, Jose A Villadangos, Jamie Rossjohn, Allison Abendroth, Barry Slobedman

JOURNAL OF INFECTIOUS DISEASES | OXFORD UNIV PRESS INC | Published : 2023

DOI: 10.1093/infdis/jiab526

Abstract

The antigen presentation molecule MR1 (major histocompatibility complex, class I–related) presents ligands derived from the riboflavin (vitamin B) synthesis pathway, which is not present in mammalian species or viruses, to mucosal-associated invariant T (MAIT) cells. In this study, we demonstrate that varicella zoster virus (VZV) profoundly suppresses MR1 expression. We show that VZV targets the intracellular reservoir of immature MR1 for degradation, while preexisting, ligand-bound cell surface MR1 is protected from such targeting, thereby highlighting an intricate temporal relationship between infection and ligand availability. We also identify VZV open reading frame (ORF) 66 as functionin..

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University of Melbourne Researchers

Hamish McWilliam Author

Jose Villadangos Author

Jamie Rossjohn Author

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DENDRITIC CELLS AND ANTIGEN PRESENTATION

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ANTIGEN PRESENTATION, RECOGNITION AND THE IMMUNE RESPONSE

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Grants

Awarded by Australian National Health and Medical Research Council (NHMRC)

Awarded by National Institutes of Health (NIH)

Awarded by Australian Research Council

Awarded by NHMRC

Awarded by NHMRC Senior Research Fellowship

Awarded by National Institute of Allergy and Infectious Diseases, NIH

Awarded by NHMRC Ideas grant

Awarded by National Health and Medical Research Council of Australia

Funding Acknowledgements

B. S., A. A., and D. C. T. are supported by the Australian National Health and Medical Research Council (NHMRC) (grant number 1126599). S. K. P. and C. S. are each a recipient of a scholarship from the Australian Government Research Training Program. P. R. K. acknowledges support from the National Institutes of Health (NIH) (grant numbers AI122640 and EY08098), and unrestricted support from the Eye and Ear Foundation of Pittsburgh and Research to Prevent Blindness Inc. J. A. V. is supported by research grants from the Australian Research Council (grant number DP170102471) and the NHMRC (grant number 1113293); an NHMRC Senior Research Fellowship (number 1058193); and the National Institute of Allergy and Infectious Diseases, NIH (grant number R01AI148407). H. E. G. M. is supported by an NHMRC Ideas grant (grant number 2003192).