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

iScience (Feb 2024)

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

Affiliations

Carolyn Samer: Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
Hamish E.G. McWilliam: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
Brian P. McSharry: Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia; School of Dentistry and Medical Sciences, Faculty of Science and Health, Charles Sturt University, Wagga Wagga, NSW, Australia
Thilaga Velusamy: John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
James G. Burchfield: Charles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, Australia
Richard J. Stanton: Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales
David C. Tscharke: John Curtin School of Medical Research, Australian National University, Canberra, ACT, Australia
Jamie Rossjohn: Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales; Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, VIC, Australia
Jose A. Villadangos: Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, VIC, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, VIC, Australia
Allison Abendroth: Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia
Barry Slobedman: Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, Australia; Corresponding author

Journal volume & issue: Vol. 27, no. 2
p. 108801

Abstract

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Summary: 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.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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