4.8 Article

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

Journal

ELIFE
Volume 9, Issue -, Pages -

Publisher

ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.48401

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Funding

  1. National Science Foundation Graduate Research Fellowship
  2. Adolph C. and Mary Sprague Miller Institute for Basic Research in Science, University of California Berkeley Postdoctoral Fellowship
  3. National Institutes of Health [R01-AI134824, 1R01AI129822-01]
  4. Singapore National Research Foundation [NRF2012NRF-CRP001-056, NRF2016NRF-NSFC002-013]
  5. Deutsche Forschungsgemeinschaft [DR 772/10-2]
  6. Bundesministerium fur Bildung und Forschung RAPID [01KI1723A]
  7. Horizon 2020 [653316]
  8. DARPA PREEMPT Program [D18AC00031]

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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.

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