A novel hamster model of SARS-CoV-2 respiratory infection using a pseudotyped virus

  1. Hiroshi Yamada
  2. So-Ichiro Sasaki
  3. Hideki Tani
  4. Mayu Somekawa
  5. Hitoshi Kawasuji
  6. Yumiko Saga
  7. Yoshihiro Yoshida
  8. Yoshihiro Yamamoto
  9. Yoshihiro Hayakawa
  10. Yoshitomo Morinaga

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Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a biosafety level (BSL)-3 pathogen; therefore, its research environment is limited. Pseudotyped viruses that mimic the infection of SARS-CoV-2 have been widely used for in vitro evaluation because they are available in BSL-2 containment laboratories. However, in vivo application is inadequate. Therefore, animal models instigated with animal BSL-2 will provide opportunities for in vivo evaluation. Hamsters (6–10-week-old males) were intratracheally inoculated with luciferase-expressing vesicular stomatitis virus (VSV)-based SARS-CoV-2 pseudotyped virus. The lungs were harvested 24–72 h after inoculation and luminescence was measured using an in vivo imaging system. Lung luminescence after inoculation with the SARS-CoV-2 pseudotyped virus increased in a dose-dependent manner and peaked at 48 h. The VSV-G (envelope G) pseudotyped virus also induced luminescence; however, a 100-fold concentration was required to reach a level similar to that of the SARS-CoV-2 pseudotyped virus. The SARS-CoV-2 pseudotyped virus is applicable to SARS-CoV-2 respiratory infections in a hamster model. Because of the single-round infectious virus, the model can be used to study the steps from viral binding to entry, which will be useful for future research on SARS-CoV-2 entry without using live SARS-CoV-2 or transgenic animals.

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  1. Version published to 10.1038/s41598-022-15258-8
  2. ScreenIT

    SciScore for 10.1101/2021.09.17.460745: (What is this?)

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

    Table 1: Rigor

    EthicsIACUC: The Ethics Review Committee for Animal Experimentation approved all experimental protocols used in the present study (Protocol Number: A2020MED-18).
    Euthanasia Agents: Bioluminescent imaging: The hamsters were sacrificed by isoflurane and cervical dislocation 24 h after infection.
    Sex as a biological variableHamster models: Male 6-to 10-week-old hamsters were purchased from Japan SLC Inc. (Shizuoka, Japan).
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Recombinant DNA
    SentencesResources
    The expression plasmid for the truncated S protein of SARS-CoV-2 and pCAG-SARS-CoV-2 S (Wuhan) was provided by Dr. Shuetsu Fukushi, National Institute of Infectious Diseases, Japan.
    pCAG-SARS-CoV-2
    suggested: None
    Pseudotyped VSVs bearing envelope (G) (VSV-G) were also generated.
    VSV-G
    suggested: RRID:Addgene_138479)
    Software and Algorithms
    SentencesResources
    Differences between low and high SARS-CoV-2pv concentrations were examined for statistical significance using an unpaired Student’s t-test with GraphPad Prism version 8.4.3 (GraphPad Software, CA).
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)
    GraphPad
    suggested: (GraphPad Prism, RRID:SCR_002798)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    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: Please consider improving the rainbow (“jet”) colormap(s) used on page 20. At least one figure is not accessible to readers with colorblindness and/or is not true to the data, i.e. not perceptually uniform.

    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.

  3. Version published to 10.1101/2021.09.17.460745v1 on bioRxiv