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Disruption of nuclear architecture as a cause of COVID-19 induced anosmia
Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using mole...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885920/ https://www.ncbi.nlm.nih.gov/pubmed/33594368 http://dx.doi.org/10.1101/2021.02.09.430314 |
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author | Zazhytska, Marianna Kodra, Albana Hoagland, Daisy A. Fullard, John F. Shayya, Hani Omer, Arina Firestein, Stuart Gong, Qizhi Canoll, Peter D. Goldman, James E. Roussos, Panos tenOever, Benjamin R. Overdevest, Jonathan B. Lomvardas, Stavros |
author_facet | Zazhytska, Marianna Kodra, Albana Hoagland, Daisy A. Fullard, John F. Shayya, Hani Omer, Arina Firestein, Stuart Gong, Qizhi Canoll, Peter D. Goldman, James E. Roussos, Panos tenOever, Benjamin R. Overdevest, Jonathan B. Lomvardas, Stavros |
author_sort | Zazhytska, Marianna |
collection | PubMed |
description | Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19. |
format | Online Article Text |
id | pubmed-7885920 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Cold Spring Harbor Laboratory |
record_format | MEDLINE/PubMed |
spelling | pubmed-78859202021-02-17 Disruption of nuclear architecture as a cause of COVID-19 induced anosmia Zazhytska, Marianna Kodra, Albana Hoagland, Daisy A. Fullard, John F. Shayya, Hani Omer, Arina Firestein, Stuart Gong, Qizhi Canoll, Peter D. Goldman, James E. Roussos, Panos tenOever, Benjamin R. Overdevest, Jonathan B. Lomvardas, Stavros bioRxiv Article Olfaction relies on a coordinated partnership between odorant flow and neuronal communication. Disruption in our ability to detect odors, or anosmia, has emerged as a hallmark symptom of infection with SARS-CoV-2, yet the mechanism behind this abrupt sensory deficit remains elusive. Here, using molecular evaluation of human olfactory epithelium (OE) from subjects succumbing to COVID-19 and a hamster model of SARS-CoV-2 infection, we discovered widespread downregulation of olfactory receptors (ORs) as well as key components of their signaling pathway. OR downregulation likely represents a non-cell autonomous effect, since SARS-CoV-2 detection in OSNs is extremely rare both in human and hamster OEs. A likely explanation for the reduction of OR transcription is the striking reorganization of nuclear architecture observed in the OSN lineage, which disrupts multi-chromosomal compartments regulating OR expression in humans and hamsters. Our experiments uncover a novel molecular mechanism by which a virus with a very selective tropism can elicit persistent transcriptional changes in cells that evade it, contributing to the severity of COVID-19. Cold Spring Harbor Laboratory 2021-02-09 /pmc/articles/PMC7885920/ /pubmed/33594368 http://dx.doi.org/10.1101/2021.02.09.430314 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (https://creativecommons.org/licenses/by-nc-nd/4.0/) , which allows reusers to copy and distribute the material in any medium or format in unadapted form only, for noncommercial purposes only, and only so long as attribution is given to the creator. |
spellingShingle | Article Zazhytska, Marianna Kodra, Albana Hoagland, Daisy A. Fullard, John F. Shayya, Hani Omer, Arina Firestein, Stuart Gong, Qizhi Canoll, Peter D. Goldman, James E. Roussos, Panos tenOever, Benjamin R. Overdevest, Jonathan B. Lomvardas, Stavros Disruption of nuclear architecture as a cause of COVID-19 induced anosmia |
title | Disruption of nuclear architecture as a cause of COVID-19 induced anosmia |
title_full | Disruption of nuclear architecture as a cause of COVID-19 induced anosmia |
title_fullStr | Disruption of nuclear architecture as a cause of COVID-19 induced anosmia |
title_full_unstemmed | Disruption of nuclear architecture as a cause of COVID-19 induced anosmia |
title_short | Disruption of nuclear architecture as a cause of COVID-19 induced anosmia |
title_sort | disruption of nuclear architecture as a cause of covid-19 induced anosmia |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7885920/ https://www.ncbi.nlm.nih.gov/pubmed/33594368 http://dx.doi.org/10.1101/2021.02.09.430314 |
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