Transmission of SARS-CoV-2 in domestic cats imposes a narrow bottleneck

  1. Katarina M. Braun
  2. Gage K. Moreno
  3. Peter J. Halfmann
  4. Emma B. Hodcroft
  5. David A. Baker
  6. Emma C. Boehm
  7. Andrea M. Weiler
  8. Amelia K. Haj
  9. Masato Hatta
  10. Shiho Chiba
  11. Tadashi Maemura
  12. Yoshihiro Kawaoka
  13. Katia Koelle
  14. David H. O’Connor
  15. Thomas C. Friedrich

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Abstract

The evolutionary mechanisms by which SARS-CoV-2 viruses adapt to mammalian hosts and, potentially, undergo antigenic evolution depend on the ways genetic variation is generated and selected within and between individual hosts. Using domestic cats as a model, we show that SARS-CoV-2 consensus sequences remain largely unchanged over time within hosts, while dynamic sub-consensus diversity reveals processes of genetic drift and weak purifying selection. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which was previously shown to confer escape from human monoclonal antibodies. This variant arises rapidly and persists at intermediate frequencies in index cats. It also becomes fixed following transmission in two of three pairs. These dynamics suggest this site may be under positive selection in this system and illustrate how a variant can quickly arise and become fixed in parallel across multiple transmission pairs. Transmission of SARS-CoV-2 in cats involved a narrow bottleneck, with new infections founded by fewer than ten viruses. In RNA virus evolution, stochastic processes like narrow transmission bottlenecks and genetic drift typically act to constrain the overall pace of adaptive evolution. Our data suggest that here, positive selection in index cats followed by a narrow transmission bottleneck may have instead accelerated the fixation of S H655Y, a potentially beneficial SARS-CoV-2 variant. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge. This underscores the importance of continued genomic surveillance for new SARS-CoV-2 variants as well as heightened scrutiny for signatures of SARS-CoV-2 positive selection in humans and mammalian model systems.

Author summary

Through ongoing human adaptation, spill-back events from other animal intermediates, or with the distribution of vaccines and therapeutics, the landscape of SARS-CoV-2 genetic variation is certain to change. The evolutionary mechanisms by which SARS-CoV-2 will continue to adapt to mammalian hosts depend on genetic variation generated within and between hosts. Here, using domestic cats as a model, we show that within-host SARS-CoV-2 genetic variation is predominantly influenced by genetic drift and purifying selection. Transmission of SARS-CoV-2 between hosts is defined by a narrow transmission bottleneck, involving 2-5 viruses. We further identify a notable variant at amino acid position 655 in Spike (H655Y), which arises rapidly and is transmitted in cats. Spike H655Y has been previously shown to confer escape from human monoclonal antibodies and is currently found in over 1000 human sequences. Overall, our study suggests species- and context-specific adaptations are likely to continue to emerge, underscoring the importance of continued genomic surveillance in humans and non-human mammalian hosts.

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  1. ScreenIT

    SciScore for 10.1101/2020.11.16.384917: (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.

    Table 2: Resources

    Software and Algorithms
    SentencesResources
    Briefly, reads are paired and merged using BBMerge (https://jgi.doe.gov/data-and-tools/bbtools/bb-tools-user-guide/bbmerge-guide/) and mapped to the reference (MW219695.1) using BBMap (https://jgi.doe.gov/data-and-tools/bbtools/bb-tools-user-guide/bbmap-guide/).
    https://jgi.doe.gov/data-and-tools/bbtools/bb-tools-user-guide/bbmerge-guide/
    suggested: (Bestus Bioinformaticus Merge, RRID:SCR_016970)
    Mapped reads were imported into Geneious (https://www.geneious.com/) for visual inspection.
    Geneious
    suggested: (Geneious, RRID:SCR_010519)
    Variants were called using callvariants.sh (contained within BBMap) and annotated using SnpEff (https://pcingola.github.io/SnpEff/).
    BBMap
    suggested: (BBmap, RRID:SCR_016965)
    SnpEff
    suggested: (SnpEff, RRID:SCR_005191)
    BBMap’s output VCF files were cleaned using custom Python scripts, which can be found in the GitHub accompanying this manuscript (https://github.com/katarinabraun/SARSCoV2_transmission_in_domestic_cats) [60].
    Python
    suggested: (IPython, RRID:SCR_001658)
    We plotted the counts of variants falling into each frequency bin using Matplotlib 3.3.2 (https://matplotlib.org).
    Matplotlib
    suggested: (MatPlotLib, RRID:SCR_008624)

    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

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  2. Version published to 10.1101/2020.11.16.384917 on bioRxiv