Cargando…
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...
Autores principales: | , , , , , , , , , , , , |
---|---|
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 |
_version_ | 1784819031802380288 |
---|---|
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. |
format | Online Article Text |
id | pubmed-9609486 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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 |
work_keys_str_mv | AT vallerianifabrizia adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT jurisiclucija adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT dipancraziochiara adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT irelliroberta adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT ciarrocchieugenia adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT martinomichele adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT coccoantonio adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT difeliceelisabetta adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT colaiannimarialoredana adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT decaronicola adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT bonfinibarbara adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT lorussoalessio adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT diteodorogiovanni adeletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT vallerianifabrizia deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT jurisiclucija deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT dipancraziochiara deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT irelliroberta deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT ciarrocchieugenia deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT martinomichele deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT coccoantonio deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT difeliceelisabetta deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT colaiannimarialoredana deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT decaronicola deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT bonfinibarbara deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT lorussoalessio deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples AT diteodorogiovanni deletionencompassingthefurincleavagesiteinthespikeencodinggenedoesnotaltersarscov2replicationinlungtissuesofminkandneutralizationbyconvalescenthumanserumsamples |