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A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples

SARS-CoV-2 has been shown to lose the furin polybasic cleavage site (FCS) following adaptation on cell culture. Deletion occurring in this region, which may include also the FCS flanking regions, seem not to affect virus replication in vitro; however, a chimeric SARS-CoV-2 virus without the sole FCS...

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Autores principales: Valleriani, Fabrizia, Jurisic, Lucija, Di Pancrazio, Chiara, Irelli, Roberta, Ciarrocchi, Eugenia, Martino, Michele, Cocco, Antonio, Di Felice, Elisabetta, Colaianni, Maria Loredana, Decaro, Nicola, Bonfini, Barbara, Lorusso, Alessio, Di Teodoro, Giovanni
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609486/
https://www.ncbi.nlm.nih.gov/pubmed/36297209
http://dx.doi.org/10.3390/pathogens11101152
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author Valleriani, Fabrizia
Jurisic, Lucija
Di Pancrazio, Chiara
Irelli, Roberta
Ciarrocchi, Eugenia
Martino, Michele
Cocco, Antonio
Di Felice, Elisabetta
Colaianni, Maria Loredana
Decaro, Nicola
Bonfini, Barbara
Lorusso, Alessio
Di Teodoro, Giovanni
author_facet Valleriani, Fabrizia
Jurisic, Lucija
Di Pancrazio, Chiara
Irelli, Roberta
Ciarrocchi, Eugenia
Martino, Michele
Cocco, Antonio
Di Felice, Elisabetta
Colaianni, Maria Loredana
Decaro, Nicola
Bonfini, Barbara
Lorusso, Alessio
Di Teodoro, Giovanni
author_sort Valleriani, Fabrizia
collection PubMed
description SARS-CoV-2 has been shown to lose the furin polybasic cleavage site (FCS) following adaptation on cell culture. Deletion occurring in this region, which may include also the FCS flanking regions, seem not to affect virus replication in vitro; however, a chimeric SARS-CoV-2 virus without the sole FCS motif has been associated with lower virulence in mice and lower neutralization values. Moreover, SARS-CoV-2 virus lacking the FCS was shed to lower titers from experimentally infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus. In this study, we investigated the replication kinetics and cellular tropism of a SARS-CoV-2 isolate carrying a 10-amino acid deletion in the spike protein spanning the FCS in lung ex vivo organ cultures of mink. Furthermore, we tested the neutralization capabilities of human convalescent SARS-CoV-2 positive serum samples against this virus. We showed that this deletion did not significantly hamper neither ex vivo replication nor neutralization activity by convalescent serum samples. This study highlights the importance of the preliminary phenotypic characterization of emerging viruses in ex vivo models and demonstrates that mink lung tissues are permissive to the replication of a mutant form of SARS-CoV-2 showing a deletion spanning the FCS. Notably, we also highlight the need for sequencing viral stocks before any infection study as large deletions may occur leading to the misinterpretation of results.
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spelling pubmed-96094862022-10-28 A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples Valleriani, Fabrizia Jurisic, Lucija Di Pancrazio, Chiara Irelli, Roberta Ciarrocchi, Eugenia Martino, Michele Cocco, Antonio Di Felice, Elisabetta Colaianni, Maria Loredana Decaro, Nicola Bonfini, Barbara Lorusso, Alessio Di Teodoro, Giovanni Pathogens Article SARS-CoV-2 has been shown to lose the furin polybasic cleavage site (FCS) following adaptation on cell culture. Deletion occurring in this region, which may include also the FCS flanking regions, seem not to affect virus replication in vitro; however, a chimeric SARS-CoV-2 virus without the sole FCS motif has been associated with lower virulence in mice and lower neutralization values. Moreover, SARS-CoV-2 virus lacking the FCS was shed to lower titers from experimentally infected ferrets and was not transmitted to cohoused sentinel animals, unlike wild-type virus. In this study, we investigated the replication kinetics and cellular tropism of a SARS-CoV-2 isolate carrying a 10-amino acid deletion in the spike protein spanning the FCS in lung ex vivo organ cultures of mink. Furthermore, we tested the neutralization capabilities of human convalescent SARS-CoV-2 positive serum samples against this virus. We showed that this deletion did not significantly hamper neither ex vivo replication nor neutralization activity by convalescent serum samples. This study highlights the importance of the preliminary phenotypic characterization of emerging viruses in ex vivo models and demonstrates that mink lung tissues are permissive to the replication of a mutant form of SARS-CoV-2 showing a deletion spanning the FCS. Notably, we also highlight the need for sequencing viral stocks before any infection study as large deletions may occur leading to the misinterpretation of results. MDPI 2022-10-06 /pmc/articles/PMC9609486/ /pubmed/36297209 http://dx.doi.org/10.3390/pathogens11101152 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Valleriani, Fabrizia
Jurisic, Lucija
Di Pancrazio, Chiara
Irelli, Roberta
Ciarrocchi, Eugenia
Martino, Michele
Cocco, Antonio
Di Felice, Elisabetta
Colaianni, Maria Loredana
Decaro, Nicola
Bonfini, Barbara
Lorusso, Alessio
Di Teodoro, Giovanni
A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples
title A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples
title_full A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples
title_fullStr A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples
title_full_unstemmed A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples
title_short A Deletion Encompassing the Furin Cleavage Site in the Spike Encoding Gene Does Not Alter SARS-CoV-2 Replication in Lung Tissues of Mink and Neutralization by Convalescent Human Serum Samples
title_sort deletion encompassing the furin cleavage site in the spike encoding gene does not alter sars-cov-2 replication in lung tissues of mink and neutralization by convalescent human serum samples
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9609486/
https://www.ncbi.nlm.nih.gov/pubmed/36297209
http://dx.doi.org/10.3390/pathogens11101152
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