Samer, Carolyn, McWilliam, Hamish E.G., McSharry, Brian P., Velusamy, Thilaga, Burchfield, James G., Stanton, Richard J. ![]() ![]() ![]() |
Preview |
PDF
- Published Version
Available under License Creative Commons Attribution. Download (6MB) | Preview |
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 |
Actions (repository staff only)
![]() |
Edit Item |