Varicella Zoster Virus Impairs Expression of the Nonclassical Major Histocompatibility Complex Class I–Related Gene Protein (MR1). (14th October 2021)

• Record Type: Journal Article
• Authors: Purohit, Shivam K; Samer, Carolyn; McWilliam, Hamish E G; Traves, Renee; Steain, Megan; McSharry, Brian P; Kinchington, Paul R; Tscharke, David C; Villadangos, Jose A; Rossjohn, Jamie; Abendroth, Allison; Slobedman, Barry
• Is Part Of: Journal of infectious diseases. Volume 227:Number 3(2023)
• Page Start: 391
• Page End: 401
• Publication Date: 2021-10-14
• Subjects: varicella zoster virus -- VZV -- immune modulation -- MR1; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiab526
• Languages: English
• ISSNs: 0022-1899

Abstract

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 functioning to suppress MR1 expression when this viral protein is expressed during transient transfection, but this is not apparent during infection with a VZV mutant virus lacking ORF66 expression. This indicates that VZV is likely to encode multiple viral genes that target MR1. Overall, we identify an immunomodulatory function of VZV whereby infection suppresses the MR1 biosynthesis pathway. Abstract : In this study, we demonstrate that varicella zoster virus profoundly suppresses expression of the antigen presentation molecule major histocompatibility complex, class I–related (MR1), thus identifying an additional immunomodulatory function encoded by this virus.