Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection

Samer, Carolyn, McWilliam, Hamish E.G., McSharry, Brian P., Velusamy, Thilaga, Burchfield, James G., Stanton, Richard J. ORCID: https://orcid.org/0000-0002-6799-1182, Tscharke, David C., Rossjohn, Jamie ORCID: https://orcid.org/0000-0002-2020-7522, Villadangos, Jose A., Abendroth, Allison and Slobedman, Barry 2024. Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection. iScience 27 (2) , 108801. 10.1016/j.isci.2024.108801

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Abstract

The major histocompatibility complex (MHC), Class-I-related (MR1) molecule presents microbiome-synthesized metabolites to Mucosal-associated invariant T (MAIT) cells, present at sites of herpes simplex virus (HSV) infection. During HSV type 1 (HSV-1) infection there is a profound and rapid loss of MR1, in part due to expression of unique short 3 protein. Here we show that virion host shutoff RNase protein downregulates MR1 protein, through loss of MR1 transcripts. Furthermore, a third viral protein, infected cell protein 22, also downregulates MR1, but not classical MHC-I molecules. This occurs early in the MR1 trafficking pathway through proteasomal degradation. Finally, HSV-2 infection results in the loss of MR1 transcripts, and intracellular and surface MR1 protein, comparable to that seen during HSV-1 infection. Thus HSV coordinates a multifaceted attack on the MR1 antigen presentation pathway, potentially protecting infected cells from MAIT cell T cell receptor-mediated detection at sites of primary infection and reactivation.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine Systems Immunity Research Institute (SIURI)
Publisher:	Cell Press
ISSN:	2589-0042
Funders:	MRC
Date of First Compliant Deposit:	17 January 2024
Date of Acceptance:	2 January 2024
Last Modified:	06 Feb 2024 16:47
URI:	https://orca.cardiff.ac.uk/id/eprint/165357

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