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Deprecated: Implicit conversion from float 225.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Elife 2021 ; 10 (ä): ä Nephropedia Template TP
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Human airway cells prevent SARS-CoV-2 multibasic cleavage site cell culture adaptation #MMPMID33835028
Lamers MM; Mykytyn AZ; Breugem TI; Wang Y; Wu DC; Riesebosch S; van den Doel PB; Schipper D; Bestebroer T; Wu NC; Haagmans BL
Elife 2021[Apr]; 10 (ä): ä PMID33835028show ga
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.