A mouse-adapted SARS-CoV-2 strain replicating in standard laboratory mice

  1. Xavier Montagutelli
  2. Matthieu Prot
  3. Grégory Jouvion
  4. Laurine Levillayer
  5. Laurine Conquet
  6. Edouard Reyes-Gomez
  7. Flora Donati
  8. Melanie Albert
  9. Sylvie van der Werf
  10. Jean Jaubert
  11. Etienne Simon-Lorière

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Abstract

SARS-CoV-2 has infected almost 200 million humans and caused over 4 million deaths worldwide. Evaluating countermeasures and improving our understanding of COVID-19 pathophysiology require access to animal models that replicate the hallmarks of human disease. Mouse infection with SARS-CoV-2 is limited by poor affinity between the virus spike protein and its cellular receptor ACE2. We have developed by serial passages the MACo3 virus strain which efficiently replicates in the lungs of standard mouse strains and induces age-dependent lung lesions. Compared to other mouse-adapted strains and severe mouse models, infection with MACo3 results in mild to moderate disease and will be useful to investigate the role of host genetics and other factors modulating COVID-19 severity.

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    SciScore for 10.1101/2021.07.10.451880: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    EthicsField Sample Permit: Materials and Methods: Ethics: All animal work was approved by the Institut Pasteur Ethics Committee (projects dap 200008 and dap 210050) and authorized by the French Ministry of Research under #24613 and #31816 in compliance with the European and French regulations on the protection of live vertebrates.
    IRB: Materials and Methods: Ethics: All animal work was approved by the Institut Pasteur Ethics Committee (projects dap 200008 and dap 210050) and authorized by the French Ministry of Research under #24613 and #31816 in compliance with the European and French regulations on the protection of live vertebrates.
    Euthanasia Agents: To initiate serial passages, 105 PFU of IDF0372 were first inoculated to two anesthetized (ketamine/xylazine) 17-week-old CC071 males which were euthanized by ketamine/xylazine overdose at dpi 3 to collect their lungs.
    Sex as a biological variableTo initiate serial passages, 105 PFU of IDF0372 were first inoculated to two anesthetized (ketamine/xylazine) 17-week-old CC071 males which were euthanized by ketamine/xylazine overdose at dpi 3 to collect their lungs.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cells and viruses: VeroE6 cells (African green monkey kidney cells from ATCC (CCL-81)) and DBT-mACE2 cells (a kind gift of Dr Luis Enjuanes) were maintained in Dulbecco’s Modified Eagle’s Medium (DMEM) supplemented with 10% fetal bovine serum (FBS) and penicillin/streptomycin.
    DBT-mACE2
    suggested: None
    Viruses were amplified and titrated by standard plaque forming assay on VeroE6 cells.
    VeroE6
    suggested: JCRB Cat# JCRB1819, RRID:CVCL_YQ49)
    Experimental Models: Organisms/Strains
    SentencesResources
    Mouse strains: BALB/cJRj (BALB/c) and C57BL/6JRj (C57BL/6) mice were purchased from Janvier Labs (Le Genest St Isle, France).
    BALB/cJRj
    suggested: None
    C57BL/6JRj
    suggested: None
    Further mouse adaptation was performed by passaging on 6-18 month-old BALB/c mice.
    BALB/c
    suggested: RRID:IMSR_ORNL:BALB/cRl)
    Infection experiments on BALB/c and C57BL/6 mice were performed as above with 105 PFU of MACo3 (sex, age and number of mice are indicated for each mouse group in the figure legends).
    C57BL/6
    suggested: None

    Results from OddPub: Thank you for sharing your data.

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    Results from scite Reference Check: We found no unreliable references.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2021.07.10.451880v1 on bioRxiv