SARS-CoV-2 evolution in animals suggests mechanisms for rapid variant selection

  1. Laura Bashor
  2. Roderick B. Gagne
  3. Angela Bosco-Lauth
  4. Richard Bowen
  5. Mark Stenglein
  6. Sue VandeWoude

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Abstract

SARS-CoV-2 spillback from humans into domestic and wild animals has been well-documented. We compared variants of cell culture-expanded SARS-CoV-2 inoculum and virus recovered from four species following experimental exposure. Five nonsynonymous changes in nsp12, S, N and M genes were near fixation in the inoculum, but reverted to wild-type sequences in RNA recovered from dogs, cats and hamsters within 1-3 days post-exposure. Fourteen emergent variants were detected in viruses recovered from animals, including substitutions at spike positions H69, N501, and D614, which also vary in human lineages of concern. The rapidity of in vitro and in vivo SARS-CoV-2 selection reveals residues with functional significance during host-switching, illustrating the potential for spillback reservoir hosts to accelerate evolution, and demonstrating plasticity of viral adaptation in animal models.

One-Sentence Summary

SARS-CoV-2 variants rapidly arise in non-human hosts, revealing viral evolution and potential risk for human reinfection.

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  1. ScreenIT

    SciScore for 10.1101/2021.03.05.434135: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Cell culture passage in vitro: SARS-CoV-2 strain USA-WA1/2020 (Genbank MN985325.1) was obtained (15) and passaged in E6 Vero cells a total of three times.
    Vero
    suggested: CLS Cat# 605372/p622_VERO, RRID:CVCL_0059)
    SARS-CoV-2 strain USA-WA1/2020 was expanded in Vero E6 cells, and all four species were inoculated with the same “Passage 3” viral stock.
    Vero E6
    suggested: RRID:CVCL_XD71)
    Software and Algorithms
    SentencesResources
    Briefly, data were trimmed for adapters and low quality using Cutadapt (48), followed by aligning reads to the viral reference sequence.
    Cutadapt
    suggested: (cutadapt, RRID:SCR_011841)
    Data were pre-processed for quality with GATK (49) prior to calling single nucleotide and structural variants with LoFreq (50).
    GATK
    suggested: (GATK, RRID:SCR_001876)
    LoFreq
    suggested: (LoFreq, RRID:SCR_013054)
    SnpEff and SnpSift were used to annotate variants and predict their functional effects (51,52).
    SnpEff
    suggested: (SnpEff, RRID:SCR_005191)
    SnpSift
    suggested: (SnpSift, RRID:SCR_015624)
    All SARS-CoV-2 raw sequence data used in this study will be publicly available upon publication in the NCBI SRA database under BioProject PRJNA704947.
    NCBI SRA
    suggested: None
    BioProject
    suggested: (NCBI BioProject, RRID:SCR_004801)

    Results from OddPub: Thank you for sharing your code and 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.

    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 10.1101/2021.03.05.434135 on bioRxiv