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Tunneling nanotubes provide a route for SARS-CoV-2 spreading
Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entr...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Association for the Advancement of Science
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299553/ https://www.ncbi.nlm.nih.gov/pubmed/35857849 http://dx.doi.org/10.1126/sciadv.abo0171 |
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author | Pepe, Anna Pietropaoli, Stefano Vos, Matthijn Barba-Spaeth, Giovanna Zurzolo, Chiara |
author_facet | Pepe, Anna Pietropaoli, Stefano Vos, Matthijn Barba-Spaeth, Giovanna Zurzolo, Chiara |
author_sort | Pepe, Anna |
collection | PubMed |
description | Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain. We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo–electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells. Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells. |
format | Online Article Text |
id | pubmed-9299553 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Association for the Advancement of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-92995532022-08-09 Tunneling nanotubes provide a route for SARS-CoV-2 spreading Pepe, Anna Pietropaoli, Stefano Vos, Matthijn Barba-Spaeth, Giovanna Zurzolo, Chiara Sci Adv Biomedicine and Life Sciences Neurological manifestations of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection represent a major issue in long coronavirus disease. How SARS-CoV-2 gains access to the brain and how infection leads to neurological symptoms are not clear because the principal means of viral entry by endocytosis, the angiotensin-converting enzyme 2 receptor, are barely detectable in the brain. We report that human neuronal cells, nonpermissive to infection through the endocytic pathway, can be infected when cocultured with permissive infected epithelial cells. SARS-CoV-2 induces the formation of tunneling nanotubes (TNTs) and exploits this route to spread to uninfected cells. In cellulo correlative fluorescence and cryo–electron tomography reveal that SARS-CoV-2 is associated with TNTs between permissive cells. Furthermore, multiple vesicular structures such as double-membrane vesicles, sites of viral replication, are observed inside TNTs between permissive and nonpermissive cells. Our data highlight a previously unknown mechanism of SARS-CoV-2 spreading, likely used as a route to invade nonpermissive cells and potentiate infection in permissive cells. American Association for the Advancement of Science 2022-07-20 /pmc/articles/PMC9299553/ /pubmed/35857849 http://dx.doi.org/10.1126/sciadv.abo0171 Text en Copyright © 2022 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY). https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution license (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Biomedicine and Life Sciences Pepe, Anna Pietropaoli, Stefano Vos, Matthijn Barba-Spaeth, Giovanna Zurzolo, Chiara Tunneling nanotubes provide a route for SARS-CoV-2 spreading |
title | Tunneling nanotubes provide a route for SARS-CoV-2 spreading |
title_full | Tunneling nanotubes provide a route for SARS-CoV-2 spreading |
title_fullStr | Tunneling nanotubes provide a route for SARS-CoV-2 spreading |
title_full_unstemmed | Tunneling nanotubes provide a route for SARS-CoV-2 spreading |
title_short | Tunneling nanotubes provide a route for SARS-CoV-2 spreading |
title_sort | tunneling nanotubes provide a route for sars-cov-2 spreading |
topic | Biomedicine and Life Sciences |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9299553/ https://www.ncbi.nlm.nih.gov/pubmed/35857849 http://dx.doi.org/10.1126/sciadv.abo0171 |
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