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SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways
Loss of olfactory function has been commonly reported in SARS-CoV-2 infections. Recovery from anosmia is not well understood. Previous studies showed that sustentacular cells, and occasionally olfactory sensory neurons (OSNs) in the olfactory epithelium (OE), are infected in SARS-CoV-2–infected pati...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
American Society for Clinical Investigation
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869979/ https://www.ncbi.nlm.nih.gov/pubmed/36378534 http://dx.doi.org/10.1172/jci.insight.160277 |
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author | Verma, Abhishek Kumar Zheng, Jian Meyerholz, David K. Perlman, Stanley |
author_facet | Verma, Abhishek Kumar Zheng, Jian Meyerholz, David K. Perlman, Stanley |
author_sort | Verma, Abhishek Kumar |
collection | PubMed |
description | Loss of olfactory function has been commonly reported in SARS-CoV-2 infections. Recovery from anosmia is not well understood. Previous studies showed that sustentacular cells, and occasionally olfactory sensory neurons (OSNs) in the olfactory epithelium (OE), are infected in SARS-CoV-2–infected patients and experimental animals. Here, we show that SARS-CoV-2 infection of sustentacular cells induces inflammation characterized by infiltration of myeloid cells to the olfactory epithelium and variably increased expression of proinflammatory cytokines. We observed widespread damage to, and loss of cilia on, OSNs, accompanied by downregulation of olfactory receptors and signal transduction molecules involved in olfaction. A consequence of OSN dysfunction was a reduction in the number of neurons in the olfactory bulb expressing tyrosine hydroxylase, consistent with reduced synaptic input. Resolution of the infection, inflammation, and olfactory dysfunction occurred over 3–4 weeks following infection in most but not all animals. We also observed similar patterns of OE infection and anosmia/hyposmia in mice infected with other human coronaviruses such as SARS-CoV and MERS-CoV. Together, these results define the downstream effects of sustentacular cell infection and provide insight into olfactory dysfunction in COVID-19–associated anosmia. |
format | Online Article Text |
id | pubmed-9869979 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | American Society for Clinical Investigation |
record_format | MEDLINE/PubMed |
spelling | pubmed-98699792023-02-06 SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways Verma, Abhishek Kumar Zheng, Jian Meyerholz, David K. Perlman, Stanley JCI Insight Research Article Loss of olfactory function has been commonly reported in SARS-CoV-2 infections. Recovery from anosmia is not well understood. Previous studies showed that sustentacular cells, and occasionally olfactory sensory neurons (OSNs) in the olfactory epithelium (OE), are infected in SARS-CoV-2–infected patients and experimental animals. Here, we show that SARS-CoV-2 infection of sustentacular cells induces inflammation characterized by infiltration of myeloid cells to the olfactory epithelium and variably increased expression of proinflammatory cytokines. We observed widespread damage to, and loss of cilia on, OSNs, accompanied by downregulation of olfactory receptors and signal transduction molecules involved in olfaction. A consequence of OSN dysfunction was a reduction in the number of neurons in the olfactory bulb expressing tyrosine hydroxylase, consistent with reduced synaptic input. Resolution of the infection, inflammation, and olfactory dysfunction occurred over 3–4 weeks following infection in most but not all animals. We also observed similar patterns of OE infection and anosmia/hyposmia in mice infected with other human coronaviruses such as SARS-CoV and MERS-CoV. Together, these results define the downstream effects of sustentacular cell infection and provide insight into olfactory dysfunction in COVID-19–associated anosmia. American Society for Clinical Investigation 2022-12-22 /pmc/articles/PMC9869979/ /pubmed/36378534 http://dx.doi.org/10.1172/jci.insight.160277 Text en © 2022 Verma et al. https://creativecommons.org/licenses/by/4.0/This work is licensed under the Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Research Article Verma, Abhishek Kumar Zheng, Jian Meyerholz, David K. Perlman, Stanley SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways |
title | SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways |
title_full | SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways |
title_fullStr | SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways |
title_full_unstemmed | SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways |
title_short | SARS-CoV-2 infection of sustentacular cells disrupts olfactory signaling pathways |
title_sort | sars-cov-2 infection of sustentacular cells disrupts olfactory signaling pathways |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9869979/ https://www.ncbi.nlm.nih.gov/pubmed/36378534 http://dx.doi.org/10.1172/jci.insight.160277 |
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