Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11

Summary: Appropriate cellular recognition of viruses is essential for the generation of an effective innate and adaptive immune response. Viral sensors and their downstream signaling components thus provide a crucial first line of host defense. Many of them exhibit subcellular relocalization upon ac...

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Main Authors: Benjamin J. Ravenhill, Marisa Oliveira, George Wood, Ying Di, Joanne Kite, Xinyue Wang, Colin T.R. Davies, Yongxu Lu, Robin Antrobus, Gill Elliott, Nerea Irigoyen, David J. Hughes, Paul A. Lyons, Betty Chung, Georg H.H. Borner, Michael P. Weekes
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Cell Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2211124725000348
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author Benjamin J. Ravenhill
Marisa Oliveira
George Wood
Ying Di
Joanne Kite
Xinyue Wang
Colin T.R. Davies
Yongxu Lu
Robin Antrobus
Gill Elliott
Nerea Irigoyen
David J. Hughes
Paul A. Lyons
Betty Chung
Georg H.H. Borner
Michael P. Weekes
author_facet Benjamin J. Ravenhill
Marisa Oliveira
George Wood
Ying Di
Joanne Kite
Xinyue Wang
Colin T.R. Davies
Yongxu Lu
Robin Antrobus
Gill Elliott
Nerea Irigoyen
David J. Hughes
Paul A. Lyons
Betty Chung
Georg H.H. Borner
Michael P. Weekes
author_sort Benjamin J. Ravenhill
collection DOAJ
description Summary: Appropriate cellular recognition of viruses is essential for the generation of an effective innate and adaptive immune response. Viral sensors and their downstream signaling components thus provide a crucial first line of host defense. Many of them exhibit subcellular relocalization upon activation, resulting in the expression of interferon and antiviral genes. To comprehensively identify signaling factors, we analyzed protein relocalization on a global scale during viral infection. cAMP-responsive element-binding protein (CREB)-regulated transcription coactivators 2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon infection with multiple viruses in diverse cell types. This movement was dependent on mitochondrial antiviral signaling protein (MAVS), cyclo-oxygenase proteins, and protein kinase A. A key effect of CRTC2/3 translocation is transcription of the fibro-inflammatory cytokine interleukin (IL)-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2. Nuclear translocation of CRTC2/3 is, therefore, identified as an important pathway in the context of viral infection.
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spelling doaj-art-9dbae23d645d48cf8f2e9ad46ed404472025-02-09T05:00:03ZengElsevierCell Reports2211-12472025-02-01442115263Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11Benjamin J. Ravenhill0Marisa Oliveira1George Wood2Ying Di3Joanne Kite4Xinyue Wang5Colin T.R. Davies6Yongxu Lu7Robin Antrobus8Gill Elliott9Nerea Irigoyen10David J. Hughes11Paul A. Lyons12Betty Chung13Georg H.H. Borner14Michael P. Weekes15Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKDepartment of Pathology, University of Cambridge, Cambridge, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKSir William Dunn School of Pathology, University of Oxford, Oxford, UKCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UKDepartment of Microbial Sciences, School of Biosciences, University of Surrey, Guildford, UKDepartment of Pathology, University of Cambridge, Cambridge, UKSchool of Biology, University of St. Andrews, St. Andrews, UKDepartment of Medicine, University of Cambridge, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UKDepartment of Pathology, University of Cambridge, Cambridge, UKMax Planck Institute of Biochemistry, Am Klopferspitz 18, Martinsried, GermanyCambridge Institute for Medical Research, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK; Corresponding authorSummary: Appropriate cellular recognition of viruses is essential for the generation of an effective innate and adaptive immune response. Viral sensors and their downstream signaling components thus provide a crucial first line of host defense. Many of them exhibit subcellular relocalization upon activation, resulting in the expression of interferon and antiviral genes. To comprehensively identify signaling factors, we analyzed protein relocalization on a global scale during viral infection. cAMP-responsive element-binding protein (CREB)-regulated transcription coactivators 2 and 3 (CRTC2/3) exhibited early cytoplasmic-to-nuclear translocation upon infection with multiple viruses in diverse cell types. This movement was dependent on mitochondrial antiviral signaling protein (MAVS), cyclo-oxygenase proteins, and protein kinase A. A key effect of CRTC2/3 translocation is transcription of the fibro-inflammatory cytokine interleukin (IL)-11. This may be important clinically in viral infections associated with fibrosis, including SARS-CoV-2. Nuclear translocation of CRTC2/3 is, therefore, identified as an important pathway in the context of viral infection.http://www.sciencedirect.com/science/article/pii/S2211124725000348CP: MicrobiologyCP: Cell biology
spellingShingle Benjamin J. Ravenhill
Marisa Oliveira
George Wood
Ying Di
Joanne Kite
Xinyue Wang
Colin T.R. Davies
Yongxu Lu
Robin Antrobus
Gill Elliott
Nerea Irigoyen
David J. Hughes
Paul A. Lyons
Betty Chung
Georg H.H. Borner
Michael P. Weekes
Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11
Cell Reports
CP: Microbiology
CP: Cell biology
title Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11
title_full Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11
title_fullStr Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11
title_full_unstemmed Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11
title_short Spatial proteomics identifies a CRTC-dependent viral signaling pathway that stimulates production of interleukin-11
title_sort spatial proteomics identifies a crtc dependent viral signaling pathway that stimulates production of interleukin 11
topic CP: Microbiology
CP: Cell biology
url http://www.sciencedirect.com/science/article/pii/S2211124725000348
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