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


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
09 04 2021
Historique:
received: 22 01 2021
accepted: 08 04 2021
pubmed: 10 4 2021
medline: 28 5 2021
entrez: 9 4 2021
Statut: epublish

Résumé

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.

Identifiants

pubmed: 33835028
doi: 10.7554/eLife.66815
pii: 66815
pmc: PMC8131099
doi:
pii:

Substances chimiques

Spike Glycoprotein, Coronavirus 0
spike protein, SARS-CoV-2 0
Serine Proteases EC 3.4.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Netherlands Organization for Health Research and Development
ID : 10150062010008
Organisme : PPP allowance
ID : LSHM19136
Organisme : ZonMw
ID : 10150062010008
Pays : Netherlands

Commentaires et corrections

Type : CommentIn

Informations de copyright

© 2021, Lamers et al.

Déclaration de conflit d'intérêts

ML, AM, TB, YW, DW, SR, Pv, DS, TB, NW, BH No competing interests declared

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Auteurs

Mart M Lamers (MM)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Anna Z Mykytyn (AZ)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Tim I Breugem (TI)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Yiquan Wang (Y)

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States.

Douglas C Wu (DC)

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States.

Samra Riesebosch (S)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Petra B van den Doel (PB)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Debby Schipper (D)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Theo Bestebroer (T)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

Nicholas C Wu (NC)

Department of Biochemistry, University of Illinois at Urbana-Champaign, Urbana, United States.
Center for Biophysics and Quantitative Biology, University of Illinois at Urbana-Champaign, Urbana, United States.
Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, United States.

Bart L Haagmans (BL)

Viroscience Department, Erasmus Medical Center, Rotterdam, Netherlands.

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