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Viruses 2019, 11(3), 260; https://doi.org/10.3390/v11030260

Enhanced Autophagy Contributes to Reduced Viral Infection in Black Flying Fox Cells

1
Department of Microbiology & Immunology, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
2
Infectious Diseases Directorate, Naval Medical Research Center, Silver Spring, MD 20910, USA
3
Risk Evaluation and Preparedness Program, Health and Biosecurity, CSIRO, Black Mountain 2601, Australia
4
Department of Pharmacology & Molecular Therapeutics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
5
Programme in Emerging Infectious Diseases, Duke-National University Singapore Medical School, Singapore 169857, Singapore
*
Author to whom correspondence should be addressed.
Received: 1 February 2019 / Revised: 1 March 2019 / Accepted: 8 March 2019 / Published: 14 March 2019
(This article belongs to the Special Issue Viruses and Bats 2019)
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Abstract

Bats are increasingly implicated as hosts of highly pathogenic viruses. The underlying virus–host interactions and cellular mechanisms that promote co-existence remain ill-defined, but physiological traits such as flight and longevity are proposed to drive these adaptations. Autophagy is a cellular homeostatic process that regulates ageing, metabolism, and intrinsic immune defense. We quantified basal and stimulated autophagic responses in black flying fox cells, and demonstrated that although black flying fox cells are susceptible to Australian bat lyssavirus (ABLV) infection, viral replication is dampened in these bat cells. Black flying fox cells tolerated prolonged ABLV infection with less cell death relative to comparable human cells, suggesting post-entry mechanisms interference with virus replication. An elevated basal autophagic level was observed and autophagy was induced in response to high virus doses. Pharmacological stimulation of the autophagy pathway reduced virus replication, indicating autophagy acts as an anti-viral mechanism. Enhancement of basal and virus-induced autophagy in bat cells connects related reports that long-lived species possess homeostatic processes that dampen oxidative stress and macromolecule damage. Exemplifying the potential that evolved cellular homeostatic adaptations like autophagy may secondarily act as anti-viral mechanisms, enabling bats to serve as natural hosts to an assortment of pathogenic viruses. Furthermore, our data suggest autophagy-inducing drugs may provide a novel therapeutic strategy for combating lyssavirus infection. View Full-Text
Keywords: autophagy; viruses; bats autophagy; viruses; bats
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Laing, E.D.; Sterling, S.L.; Weir, D.L.; Beauregard, C.R.; Smith, I.L.; Larsen, S.E.; Wang, L.-F.; Snow, A.L.; Schaefer, B.C.; Broder, C.C. Enhanced Autophagy Contributes to Reduced Viral Infection in Black Flying Fox Cells. Viruses 2019, 11, 260.

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