ADAM17 targeting by human cytomegalovirus remodels the cell surface proteome to simultaneously regulate multiple immune pathways.


Journal

Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876

Informations de publication

Date de publication:
15 08 2023
Historique:
medline: 14 8 2023
pubmed: 10 8 2023
entrez: 10 8 2023
Statut: ppublish

Résumé

Human cytomegalovirus (HCMV) is a major human pathogen whose life-long persistence is enabled by its remarkable capacity to systematically subvert host immune defenses. In exploring the finding that HCMV infection up-regulates tumor necrosis factor receptor 2 (TNFR2), a ligand for the pro-inflammatory antiviral cytokine TNFα, we found that the underlying mechanism was due to targeting of the protease, A Disintegrin And Metalloproteinase 17 (ADAM17). ADAM17 is the prototype 'sheddase', a family of proteases that cleaves other membrane-bound proteins to release biologically active ectodomains into the supernatant. HCMV impaired ADAM17 surface expression through the action of two virally-encoded proteins in its U

Identifiants

pubmed: 37561786
doi: 10.1073/pnas.2303155120
pmc: PMC10438378
doi:

Substances chimiques

Tumor Necrosis Factor-alpha 0
Proteome 0
Receptors, Tumor Necrosis Factor, Type II 0
Membrane Proteins 0
Cytokines 0
Metalloproteases EC 3.4.-
ADAM17 Protein EC 3.4.24.86
UL144 ORF protein, Human herpesvirus 5 0
Membrane Glycoproteins 0
Viral Proteins 0
ADAM17 protein, human EC 3.4.24.86
UL148 protein, human cytomegalovirus 0

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

e2303155120

Subventions

Organisme : Medical Research Council
ID : MR/P001602/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V000489/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/S00971X/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : MC_UU_12014/3
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 100326/Z/12/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 108070/Z/15/Z
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 207503/Z/17/Z
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/V000489/1
Pays : United Kingdom
Organisme : Wellcome Trust
ID : 204870
Pays : United Kingdom

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Auteurs

Anzelika Rubina (A)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Mihil Patel (M)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Katie Nightingale (K)

Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.

Martin Potts (M)

Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
Department of Medicine, University of Cambridge, Cambridge CB2 0XY, United Kingdom.

Ceri A Fielding (CA)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Simon Kollnberger (S)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Betty Lau (B)

Centre for Virus Research, University of Glasgow, Glasgow G12 8TA, United Kingdom.

Kristin Ladell (K)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Kelly L Miners (KL)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Jenna Nichols (J)

Centre for Virus Research, University of Glasgow, Glasgow G12 8TA, United Kingdom.

Luis Nobre (L)

Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.

Dawn Roberts (D)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Terrence M Trinca (TM)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Jason P Twohig (JP)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Virginia-Maria Vlahava (VM)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Andrew J Davison (AJ)

Centre for Virus Research, University of Glasgow, Glasgow G12 8TA, United Kingdom.

David A Price (DA)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Peter Tomasec (P)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Gavin W G Wilkinson (GWG)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Michael P Weekes (MP)

Cambridge Institute for Medical Research, University of Cambridge, Cambridge CB2 0XY, United Kingdom.
Department of Medicine, University of Cambridge, Cambridge CB2 0XY, United Kingdom.

Richard J Stanton (RJ)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

Eddie C Y Wang (ECY)

Division of Infection and Immunity, School of Medicine, Cardiff University, Cardiff CF14 4XN, United Kingdom.

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Classifications MeSH