Journal article

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

C Samer, HEG McWilliam, BP McSharry, JG Burchfield, RJ Stanton, J Rossjohn, JA Villadangos, A Abendroth, B Slobedman

Journal of Biological Chemistry | ELSEVIER | Published : 2024

Abstract

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 ..

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Grants

Awarded by University of Sydney


Funding Acknowledgements

C. S. was supported by an Australian Postgraduate Award/Australian Government Research Training Program Scholarship. We acknowledge grant support from the National Health and Medical Research Council (NHMRC) of Australia, 198704 (A. A. and B. S.) , 2003192 (H. E. G. M.) , 2013621 (J. G. B.) , and 1113293 and 1154502 (J. A. V.) , the US National Institutes of Health RO1 R01AI148407 (J. R. and J. A. V.) , NHMRC Leadership Investigator grants 2008913 (J. R.) and 2016969 (J. A. V.) , Australian Research Council (ARC) DP170102471 (J. A. V.) , Wellcome Trust 226615/Z/22/Z (R. J. S.) , and UK Medical Research Council (MRC) MR/S00971X/1 (R. J. S.) . The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.