Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation

Virus propagation methods generally use transformed cell lines to grow viruses from clinical specimens, which may force viruses to rapidly adapt to cell culture conditions, a process facilitated by high viral mutation rates. Upon propagation in VeroE6 cells, SARS-CoV-2 may mutate or delete the multi...

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Bibliographic Details
Published in:eLife 2021-04, Vol.10
Main Authors: Lamers, Mart M, Mykytyn, Anna Z, Breugem, Tim I, Wang, Yiquan, Wu, Douglas C, Riesebosch, Samra, van den Doel, Petra B, Schipper, Debby, Bestebroer, Theo, Wu, Nicholas C, Haagmans, Bart L
Format: Article
Language:English
Subjects:
Adaptation
airway organoids
Amino acids
Cell culture
cell culture adaptation
Cell lines
Coronaviruses
COVID-19
furin cleavage site
Health aspects
Microbiology and Infectious Disease
Mutation
Mutation rates
Organoids
Propagation
Proteases
Research Advance
Respiratory tract
SARS-CoV-2
Serine
serine proteases
Serine proteinase
Severe acute respiratory syndrome coronavirus 2
Spike protein
Viruses
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Summary:Virus propagation methods generally use transformed cell lines to grow viruses from clinical specimens, which may force viruses to rapidly adapt to cell culture conditions, a process facilitated by high viral mutation rates. Upon propagation in VeroE6 cells, SARS-CoV-2 may mutate or delete the multibasic cleavage site (MBCS) in the spike protein. Previously, we showed that the MBCS facilitates serine protease-mediated entry into human airway cells (Mykytyn et al., 2021). Here, we report that propagating SARS-CoV-2 on the human airway cell line Calu-3 - that expresses serine proteases - prevents cell culture adaptations in the MBCS and directly adjacent to the MBCS (S686G). Similar results were obtained using a human airway organoid-based culture system for SARS-CoV-2 propagation. Thus, in-depth knowledge on the biology of a virus can be used to establish methods to prevent cell culture adaptation.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.66815