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Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions

Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellu...

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Autores principales: Liu, Shu, Hossinger, André, Heumüller, Stefanie-Elisabeth, Hornberger, Annika, Buravlova, Oleksandra, Konstantoulea, Katerina, Müller, Stephan A., Paulsen, Lydia, Rousseau, Frederic, Schymkowitz, Joost, Lichtenthaler, Stefan F., Neumann, Manuela, Denner, Philip, Vorberg, Ina M.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526834/
https://www.ncbi.nlm.nih.gov/pubmed/34667166
http://dx.doi.org/10.1038/s41467-021-25855-2
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author Liu, Shu
Hossinger, André
Heumüller, Stefanie-Elisabeth
Hornberger, Annika
Buravlova, Oleksandra
Konstantoulea, Katerina
Müller, Stephan A.
Paulsen, Lydia
Rousseau, Frederic
Schymkowitz, Joost
Lichtenthaler, Stefan F.
Neumann, Manuela
Denner, Philip
Vorberg, Ina M.
author_facet Liu, Shu
Hossinger, André
Heumüller, Stefanie-Elisabeth
Hornberger, Annika
Buravlova, Oleksandra
Konstantoulea, Katerina
Müller, Stephan A.
Paulsen, Lydia
Rousseau, Frederic
Schymkowitz, Joost
Lichtenthaler, Stefan F.
Neumann, Manuela
Denner, Philip
Vorberg, Ina M.
author_sort Liu, Shu
collection PubMed
description Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contribute to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell contact or via EV depends on receptor-ligand interactions. We hypothesized that enabling these interactions through viral ligands enhances intercellular proteopathic seed transmission. Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. Thus, receptor-ligand interactions are important determinants of intercellular aggregate dissemination. Our data raise the possibility that viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer.
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spelling pubmed-85268342021-10-22 Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions Liu, Shu Hossinger, André Heumüller, Stefanie-Elisabeth Hornberger, Annika Buravlova, Oleksandra Konstantoulea, Katerina Müller, Stephan A. Paulsen, Lydia Rousseau, Frederic Schymkowitz, Joost Lichtenthaler, Stefan F. Neumann, Manuela Denner, Philip Vorberg, Ina M. Nat Commun Article Protein aggregates associated with neurodegenerative diseases have the ability to transmit to unaffected cells, thereby templating their own aberrant conformation onto soluble homotypic proteins. Proteopathic seeds can be released into the extracellular space, secreted in association with extracellular vesicles (EV) or exchanged by direct cell-to-cell contact. The extent to which each of these pathways contribute to the prion-like spreading of protein misfolding is unclear. Exchange of cellular cargo by both direct cell contact or via EV depends on receptor-ligand interactions. We hypothesized that enabling these interactions through viral ligands enhances intercellular proteopathic seed transmission. Using different cellular models propagating prions or pathogenic Tau aggregates, we demonstrate that vesicular stomatitis virus glycoprotein and SARS-CoV-2 spike S increase aggregate induction by cell contact or ligand-decorated EV. Thus, receptor-ligand interactions are important determinants of intercellular aggregate dissemination. Our data raise the possibility that viral infections contribute to proteopathic seed spreading by facilitating intercellular cargo transfer. Nature Publishing Group UK 2021-10-19 /pmc/articles/PMC8526834/ /pubmed/34667166 http://dx.doi.org/10.1038/s41467-021-25855-2 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Liu, Shu
Hossinger, André
Heumüller, Stefanie-Elisabeth
Hornberger, Annika
Buravlova, Oleksandra
Konstantoulea, Katerina
Müller, Stephan A.
Paulsen, Lydia
Rousseau, Frederic
Schymkowitz, Joost
Lichtenthaler, Stefan F.
Neumann, Manuela
Denner, Philip
Vorberg, Ina M.
Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
title Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
title_full Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
title_fullStr Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
title_full_unstemmed Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
title_short Highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
title_sort highly efficient intercellular spreading of protein misfolding mediated by viral ligand-receptor interactions
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8526834/
https://www.ncbi.nlm.nih.gov/pubmed/34667166
http://dx.doi.org/10.1038/s41467-021-25855-2
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