Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2024-02-01
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| Series: | iScience |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2589004224000221 |
| _version_ | 1827378190263255040 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Carolyn Samer |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T12:52:23Z |
| format | Article |
| id | doaj.art-6e9ab8496a94412f99c1c5df7b46f8e0 |
| institution | Directory Open Access Journal |
| issn | 2589-0042 |
| language | English |
| last_indexed | 2024-03-08T12:52:23Z |
| publishDate | 2024-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj.art-6e9ab8496a94412f99c1c5df7b46f8e02024-01-20T04:46:11ZengElsevieriScience2589-00422024-02-01272108801Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infectionCarolyn Samer0Hamish E.G. McWilliam1Brian P. McSharry2Thilaga Velusamy3James G. Burchfield4Richard J. Stanton5David C. Tscharke6Jamie Rossjohn7Jose A. Villadangos8Allison Abendroth9Barry Slobedman10Infection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaDepartment 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, AustraliaInfection, 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, AustraliaJohn Curtin School of Medical Research, Australian National University, Canberra, ACT, AustraliaCharles Perkins Centre, The University of Sydney, Sydney, NSW, Australia; School of Life and Environmental Sciences, University of Sydney, Sydney, NSW, AustraliaDivision of Infection & Immunity, School of Medicine, Cardiff University, Cardiff, WalesJohn Curtin School of Medical Research, Australian National University, Canberra, ACT, AustraliaDivision 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, AustraliaDepartment 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, AustraliaInfection, Immunity and Inflammation, School of Medical Sciences, Faculty of Medicine and Health, and the Charles Perkins Centre, The University of Sydney, Camperdown, NSW, AustraliaInfection, 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 authorSummary: 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.http://www.sciencedirect.com/science/article/pii/S2589004224000221Cell biologyImmunologyVirology |
| spellingShingle | 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 Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection iScience Cell biology Immunology Virology |
| title | Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection |
| title_full | Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection |
| title_fullStr | Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection |
| title_full_unstemmed | Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection |
| title_short | Multi-targeted loss of the antigen presentation molecule MR1 during HSV-1 and HSV-2 infection |
| title_sort | multi targeted loss of the antigen presentation molecule mr1 during hsv 1 and hsv 2 infection |
| topic | Cell biology Immunology Virology |
| url | http://www.sciencedirect.com/science/article/pii/S2589004224000221 |
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