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Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells

The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demo...

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Autores principales: Nelli, Rahul K., Phadke, Kruttika-S, Castillo, Gino, Yen, Lu, Saunders, Amy, Rauh, Rolf, Nelson, William, Bellaire, Bryan H., Giménez-Lirola, Luis G.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661338/
https://www.ncbi.nlm.nih.gov/pubmed/34893585
http://dx.doi.org/10.1038/s41420-021-00781-w
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author Nelli, Rahul K.
Phadke, Kruttika-S
Castillo, Gino
Yen, Lu
Saunders, Amy
Rauh, Rolf
Nelson, William
Bellaire, Bryan H.
Giménez-Lirola, Luis G.
author_facet Nelli, Rahul K.
Phadke, Kruttika-S
Castillo, Gino
Yen, Lu
Saunders, Amy
Rauh, Rolf
Nelson, William
Bellaire, Bryan H.
Giménez-Lirola, Luis G.
author_sort Nelli, Rahul K.
collection PubMed
description The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demonstrate clinical signs and transmission between pigs, while later attempts using a higher infectious dose reported viral shedding and seroconversion. This study investigated species-specific cell susceptibility, virus dose-dependent infectivity, and infection kinetics, using primary human (HRECs) and porcine (PRECs) respiratory epithelial cells. Despite higher ACE2 expression in HRECs compared to PRECs, SARS-CoV-2 infected, and replicated in both PRECs and HRECs in a dose-dependent manner. Cytopathic effect was particularly more evident in PRECs than HRECs, showing the hallmark morphological signs of apoptosis. Further analysis confirmed an early and enhanced apoptotic mechanism driven through caspase 3/7 activation, limiting SARS-CoV-2 propagation in PRECs compared to HRECs. Our findings shed light on a possible mechanism of resistance of pigs to SARS-CoV-2 infection, and it may hold therapeutic value for the treatment of COVID-19.
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spelling pubmed-86613382021-12-10 Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells Nelli, Rahul K. Phadke, Kruttika-S Castillo, Gino Yen, Lu Saunders, Amy Rauh, Rolf Nelson, William Bellaire, Bryan H. Giménez-Lirola, Luis G. Cell Death Discov Article The ability of SARS-CoV to infect different species, including humans, dogs, cats, minks, ferrets, hamsters, tigers, and deer, pose a continuous threat to human and animal health. Pigs, though closely related to humans, seem to be less susceptible to SARS-CoV-2. Former in vivo studies failed to demonstrate clinical signs and transmission between pigs, while later attempts using a higher infectious dose reported viral shedding and seroconversion. This study investigated species-specific cell susceptibility, virus dose-dependent infectivity, and infection kinetics, using primary human (HRECs) and porcine (PRECs) respiratory epithelial cells. Despite higher ACE2 expression in HRECs compared to PRECs, SARS-CoV-2 infected, and replicated in both PRECs and HRECs in a dose-dependent manner. Cytopathic effect was particularly more evident in PRECs than HRECs, showing the hallmark morphological signs of apoptosis. Further analysis confirmed an early and enhanced apoptotic mechanism driven through caspase 3/7 activation, limiting SARS-CoV-2 propagation in PRECs compared to HRECs. Our findings shed light on a possible mechanism of resistance of pigs to SARS-CoV-2 infection, and it may hold therapeutic value for the treatment of COVID-19. Nature Publishing Group UK 2021-12-10 /pmc/articles/PMC8661338/ /pubmed/34893585 http://dx.doi.org/10.1038/s41420-021-00781-w 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
Nelli, Rahul K.
Phadke, Kruttika-S
Castillo, Gino
Yen, Lu
Saunders, Amy
Rauh, Rolf
Nelson, William
Bellaire, Bryan H.
Giménez-Lirola, Luis G.
Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
title Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
title_full Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
title_fullStr Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
title_full_unstemmed Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
title_short Enhanced apoptosis as a possible mechanism to self-limit SARS-CoV-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
title_sort enhanced apoptosis as a possible mechanism to self-limit sars-cov-2 replication in porcine primary respiratory epithelial cells in contrast to human cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8661338/
https://www.ncbi.nlm.nih.gov/pubmed/34893585
http://dx.doi.org/10.1038/s41420-021-00781-w
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