Impaired endocytosis and accumulation in early endosomal compartments defines herpes simplex virus-mediated disruption of the nonclassical MHC class I-related molecule MR1.

Autor:	Samer C; Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia., McWilliam HEG; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia., McSharry BP; Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia; School of Dentistry and Medical Sciences, Faculty of Science and Health, and Gulbali Institute, Charles Sturt University, Wagga Wagga, New South Wales, Australia., Burchfield JG; Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia; School of Life and Environmental Sciences, The University of Sydney, Camperdown, New South Wales, Australia., Stanton RJ; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK., Rossjohn J; Division of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, Wales, UK; Infection and Immunity Program, Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute, Monash University, Clayton, Victoria, Australia., Villadangos JA; Department of Microbiology and Immunology, Peter Doherty Institute for Infection and Immunity, The University of Melbourne, Melbourne, Victoria, Australia; Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, The University of Melbourne, Parkville, Victoria, Australia., Abendroth A; Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia., Slobedman B; Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, New South Wales, Australia. Electronic address: barry.slobedman@sydney.edu.au.
Jazyk:	angličtina
Zdroj:	The Journal of biological chemistry [J Biol Chem] 2024 Oct; Vol. 300 (10), pp. 107748. Date of Electronic Publication: 2024 Sep 12.
DOI:	10.1016/j.jbc.2024.107748
Abstrakt:	Presentation of metabolites by the major histocompatibility complex class I-related protein 1 (MR1) molecule to mucosal-associated invariant T cells is impaired during herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections. This is surprising given these viruses do not directly synthesise MR1 ligands. We have previously identified several HSV proteins responsible for rapidly downregulating the intracellular pool of immature MR1, effectively inhibiting new surface antigen presentation, while preexisting ligand-bound mature MR1 is unexpectedly upregulated by HSV-1. Using flow cytometry, immunoblotting, and high-throughput fluorescence microscopy, we demonstrate that the endocytosis of surface MR1 is impaired during HSV infection and that internalized molecules accumulate in EEA1-labeled early endosomes, avoiding degradation. We establish that the short MR1 cytoplasmic tail is not required for HSV-1-mediated downregulation of immature molecules; however it may play a role in the retention of mature molecules on the surface and in early endosomes. We also determine that the HSV-1 US3 protein, the shorter US3.5 kinase and the full-length HSV-2 homolog, all predominantly target mature surface rather than total MR1 levels. We propose that the downregulation of intracellular and cell surface MR1 molecules by US3 and other HSV proteins is an immune-evasive countermeasure to minimize the effect of impaired MR1 endocytosis, which might otherwise render infected cells susceptible to MR1-mediated killing by mucosal-associated invariant T cells. Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article. (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu