Accelerated viral dynamics in bat cell lines, with implications for zoonotic emergence
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.
Article and author information
Author details
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
- Dan Haydon, University of Glasgow, United Kingdom
Publication history
- Received: May 13, 2019
- Accepted: February 2, 2020
- Accepted Manuscript published: February 3, 2020 (version 1)
- Version of Record published: March 10, 2020 (version 2)
- 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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