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

AI Article Synopsis

  • Virus propagation in transformed cell lines can lead to rapid adaptations in viruses due to their high mutation rates, as seen with SARS-CoV-2.
  • Research shows that using human airway cells like Calu-3, which express serine proteases, helps prevent mutations or deletions in critical viral protein regions during propagation.
  • This demonstrates that understanding a virus's biology can inform strategies to minimize unwanted changes when growing it in lab settings.

Article 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.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8131099PMC
http://dx.doi.org/10.7554/eLife.66815DOI Listing

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