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SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology

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Ogando, Natacha S., Dalebout, Tim J., Zevenhoven-Dobbe, Jessika C., Limpens, Ronald W.A.L., van der Meer, Yvonne, Caly, Leon, Druce, Julian, de Vries, Jutte J. C., Kikkert, Marjolein, Bárcena, Montserrat, Sidorov, Igor, Snijder, Eric J.·2020·Journal of General Virology
DOI 10.1099/jgv.0.001453

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Abstract

The sudden emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) at the end of 2019 from the Chinese province of Hubei and its subsequent pandemic spread highlight the importance of understanding the full molecular details of coronavirus infection and pathogenesis. Here, we compared a variety of replication features of SARS-CoV-2 and SARS-CoV and analysed the cytopathology caused by the two closely related viruses in the commonly used Vero E6 cell line. Compared to SARS-CoV, SARS-CoV-2 generated higher levels of intracellular viral RNA, but strikingly about 50-fold less infectious viral progeny was recovered from the culture medium. Immunofluorescence microscopy of SARS-CoV-2-infected cells established extensive cross-reactivity of antisera previously raised against a variety of non-structural proteins, membrane and nucleocapsid protein of SARS-CoV. Electron microscopy revealed that the ultrastructural changes induced by the two SARS viruses are very similar and occur within comparable time frames after infection. Furthermore, we determined that the sensitivity of the two viruses to three established inhibitors of coronavirus replication (remdesivir, alisporivir and chloroquine) is very similar, but that SARS-CoV-2 infection was substantially more sensitive to pre-treatment of cells with pegylated interferon alpha. An important difference between the two viruses is the fact that – upon passaging in Vero E6 cells – SARS-CoV-2 apparently is under strong selection pressure to acquire adaptive mutations in its spike protein gene. These mutations change or delete a putative furin-like cleavage site in the region connecting the S1 and S2 domains and result in a very prominent phenotypic change in plaque assays.

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Metadata

Authors
Ogando, N. S., Dalebout, T. J., Zevenhoven-Dobbe, J. C., Limpens, R. W. A. L., van der Meer, Y., Caly, L., Druce, J., de Vries, J. J. C., Kikkert, M., Bárcena, M., Sidorov, I., & Snijder, E. J.
Venue
Journal of General Virology
Publisher
Microbiology Society
Published
2020-09-01
Volume
101
Issue
9
Pages
925-940
ISSN
  • 0022-1317 (ISSN-L)
  • 1465-2099
DOI
10.1099/jgv.0.001453
OpenAlex
W3036391214
Cited by
551
References
9
FWCI
12.80
Type
journal article
Language
en
Open access
hybrid
Licence
creativecommons.org/licenses/by/4.0/ (unspecified)

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CoChat. (2026). Citation check: SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. https://app.cochat.ai/papers/10.1099/jgv.0.001453
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Ogando, N. S., Dalebout, T. J., Zevenhoven-Dobbe, J. C., Limpens, R. W. A. L., van der Meer, Y., Caly, L., Druce, J., de Vries, J. J. C., Kikkert, M., Bárcena, M., Sidorov, I., & Snijder, E. J. (2020). SARS-coronavirus-2 replication in Vero E6 cells: replication kinetics, rapid adaptation and cytopathology. Journal of General Virology. https://doi.org/10.1099/jgv.0.001453

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Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.