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.
D614G
SARS-CoV-2
furin cleavage site deletion
minks
neutralization
respiratory ex vivo organ culture
viral replication
Journal
Pathogens (Basel, Switzerland)
ISSN: 2076-0817
Titre abrégé: Pathogens
Pays: Switzerland
ID NLM: 101596317
Informations de publication
Date de publication:
06 Oct 2022
06 Oct 2022
Historique:
received:
31
08
2022
revised:
26
09
2022
accepted:
03
10
2022
entrez:
27
10
2022
pubmed:
28
10
2022
medline:
28
10
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36297209
pii: pathogens11101152
doi: 10.3390/pathogens11101152
pmc: PMC9609486
pii:
doi:
Types de publication
Journal Article
Langues
eng
Subventions
Organisme : European Union
ID : 773830
Organisme : Italian Ministry of Health
ID : MSRCTE0520
Organisme : Italian Ministry of Health
ID : PRC2020101 STRATEGIC
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