Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence

  1. Cara E Brook  Is a corresponding author
  2. Mike Boots
  3. Kartik Chandran
  4. Andrew P Dobson
  5. Christian Drosten
  6. Andrea L Graham
  7. Bryan T Grenfell
  8. Marcel A Müller
  9. Melinda Ng
  10. Lin-Fa Wang
  11. Anieke van Leeuwen
  1. University of California, Berkeley, United States
  2. Albert Einstein College Of Medicine, United States
  3. Princeton University, United States
  4. Charité Universitätsmedizin, Germany
  5. Albert Einstein College of Medicine, United States
  6. Duke-National University of Singapore Medical School, Singapore
  7. Royal Netherlands Institute for Sea Research, Netherlands

Abstract

Bats host virulent zoonotic viruses without experiencing disease. A mechanistic understanding of the impact of bats' virus hosting capacities, including uniquely constitutive immune pathways, on cellular-scale viral dynamics is needed to elucidate zoonotic emergence. We carried out virus infectivity assays on bat cell lines expressing induced and constitutive immune phenotypes, then developed a theoretical model of our in vitro system, which we fit to empirical data. Best fit models recapitulated expected immune phenotypes for representative cell lines, supporting robust antiviral defenses in bat cells that correlated with higher estimates for within-host viral propagation rates. In general, heightened immune responses limit pathogen-induced cellular morbidity, which can facilitate the establishment of rapidly-propagating persistent infections within-host. Rapidly-replicating viruses that have evolved with bat immune systems will likely cause enhanced virulence following emergence into secondary hosts with immune systems that diverge from those unique to bats.

Data availability

All data generated or analysed during this study are included in the manuscript and supporting files. All images and code used in this study have been made available for download at the following Figshare repository: 10.6084/m9.figshare.8312807.

The following data sets were generated

Article and author information

Author details

  1. Cara E Brook

    Department of Integrative Biology, University of California, Berkeley, Berkeley, United States
    For correspondence
    cbrook@berkeley.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4276-073X
  2. Mike Boots

    Department of Integrative Biology, University of California, Berkeley, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Kartik Chandran

    Department of Microbiology and Immunology, Albert Einstein College Of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-0232-7077
  4. Andrew P Dobson

    Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Christian Drosten

    Institute of Virology, Charité Universitätsmedizin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
  6. Andrea L Graham

    Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6580-2755
  7. Bryan T Grenfell

    Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States
    Competing interests
    The authors declare that no competing interests exist.
  8. Marcel A Müller

    Institute of Virology, Charité Universitätsmedizin, Berlin, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2242-5117
  9. Melinda Ng

    Department of Microbiology and Immunology, Albert Einstein College of Medicine, New York, United States
    Competing interests
    The authors declare that no competing interests exist.
  10. Lin-Fa Wang

    Program in Emerging Infectious Diseases, Duke-National University of Singapore Medical School, Singapore, Singapore
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-2752-0535
  11. Anieke van Leeuwen

    Department of Coastal Systems, Royal Netherlands Institute for Sea Research, Texel, Netherlands
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1987-1458

Funding

National Science Foundation (Graduate Research Fellowship)

  • Cara E Brook

Adolph C. and Mary Sprague Miller Institute for Basic Research in Science, University of California Berkeley (Postdoctoral Fellowship)

  • Cara E Brook

National Institutes of Health (R01-AI134824)

  • Kartik Chandran

Singapore National Research Foundation Grant (NRF2012NRF-CRP001-056)

  • Lin-Fa Wang

Singapore National Research Foundation Grant (NRF2016NRF-NSFC002-013)

  • Lin-Fa Wang

Deutsche Forschungsgemeinschaft (DR 772/10-2)

  • Marcel A Müller

German Federal Ministry of Education and Research (RAPID #01KI1723A)

  • Marcel A Müller

European Union Horizon Grant 2020 (#653316)

  • Marcel A Müller

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Dan Haydon, University of Glasgow, United Kingdom

Publication history

  1. Received: May 13, 2019
  2. Accepted: February 2, 2020
  3. Accepted Manuscript published: February 3, 2020 (version 1)
  4. Version of Record published: March 10, 2020 (version 2)
  5. Version of Record updated: March 12, 2020 (version 3)

Copyright

© 2020, Brook et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Cara E Brook
  2. Mike Boots
  3. Kartik Chandran
  4. Andrew P Dobson
  5. Christian Drosten
  6. Andrea L Graham
  7. Bryan T Grenfell
  8. Marcel A Müller
  9. Melinda Ng
  10. Lin-Fa Wang
  11. Anieke van Leeuwen
(2020)
Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence
eLife 9:e48401.
https://doi.org/10.7554/eLife.48401

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