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

Author:

Brook Cara E12ORCID,Boots Mike1,Chandran Kartik3ORCID,Dobson Andrew P2,Drosten Christian4,Graham Andrea L2ORCID,Grenfell Bryan T25,Müller Marcel A46ORCID,Ng Melinda3,Wang Lin-Fa7ORCID,van Leeuwen Anieke28ORCID

Affiliation:

1. Department of Integrative Biology, University of California, Berkeley, Berkeley, United States

2. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, United States

3. Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, United States

4. Institute of Virology, Charité-Universitätsmedizin Berlin, corporate member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany

5. Fogarty International Center, National Institutes of Health, Bethesda, United States

6. Martsinovsky Institute of Medical Parasitology, Tropical and Vector Borne Diseases, Sechenov University, Moscow, Russian Federation

7. Emerging Infectious Diseases Program, Duke-National University of Singapore Medical School, Singapore, Singapore

8. Royal Netherlands Institute for Sea Research, Department of Coastal Systems, and Utrecht University, Den Burg, 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-transmitting 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.

Funder

National Science Foundation

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

National Institutes of Health

Singapore National Research Foundation

Deutsche Forschungsgemeinschaft

Bundesministerium für Bildung und Forschung

Horizon 2020

DARPA

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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