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

Carolyn Samer, Hamish E.G. McWilliam, Brian P. McSharry, Thilaga Velusamy, James G. Burchfield, Richard J. Stanton, David C. Tscharke, Jamie Rossjohn, Jose A. Villadangos, Allison Abendroth, Barry Slobedman

Research output: Contribution to journalArticlepeer-review

23 Downloads (Pure)


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.
Original languageEnglish
Article number108801
Issue number2
Publication statusPublished - 16 Feb 2024


Dive into the research topics of 'Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection'. Together they form a unique fingerprint.

Cite this