Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation.
Elife, 2021/04/09;10
Lamers MM[1], Mykytyn AZ[1], Breugem TI[1], Wang Y[2], Wu DC[2], Riesebosch S[1], van den Doel PB[1], Schipper D[1], Bestebroer T[1], Wu NC[2, 3, 4], Haagmans BL[1]
Affiliations
PMID: 33835028
Impact factor: 8.713
Abstract
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.
Keywords: COVID-19; SARS-CoV-2; airway organoids; cell culture adaptation; furin cleavage site; infectious disease; microbiology; serine proteases; virus
MeSH terms
Animals; Cell Line; Chlorocebus aethiops; Epithelial Cells; Humans; Proteolysis; Respiratory System; SARS-CoV-2; Serine Proteases; Spike Glycoprotein, Coronavirus; Virus Cultivation; Virus Internalization
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