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Viruses 2019, 11(2), 152; https://doi.org/10.3390/v11020152

Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat

1
Department of Veterinary Microbiology, Western College of Veterinary Medicine, University of Saskatchewan, Saskatoon, SK S7N 5B4, Canada
2
Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-Intervac), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada
*
Author to whom correspondence should be addressed.
Current affiliation: Department of Pathology and Molecular Medicine, Michael DeGroote Institute for Infectious Disease Research, McMaster University, Hamilton, ON L8S 4L8, Canada.
Received: 10 December 2018 / Revised: 8 February 2019 / Accepted: 11 February 2019 / Published: 13 February 2019
(This article belongs to the Special Issue Viruses and Bats 2019)
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Abstract

Insectivorous bats are speculated to be ancestral hosts of Middle-East respiratory syndrome (MERS) coronavirus (CoV). MERS-CoV causes disease in humans with thirty-five percent fatality, and has evolved proteins that counteract human antiviral responses. Since bats experimentally infected with MERS-CoV do not develop signs of disease, we tested the hypothesis that MERS-CoV would replicate less efficiently in bat cells than in human cells because of its inability to subvert antiviral responses in bat cells. We infected human and bat (Eptesicus fuscus) cells with MERS-CoV and observed that the virus grew to higher titers in human cells. MERS-CoV also effectively suppressed the antiviral interferon beta (IFNβ) response in human cells, unlike in bat cells. To determine if IRF3, a critical mediator of the interferon response, also regulated the response in bats, we examined the response of IRF3 to poly(I:C), a synthetic analogue of viral double-stranded RNA. We observed that bat IRF3 responded to poly(I:C) by nuclear translocation and post-translational modifications, hallmarks of IRF3 activation. Suppression of IRF3 by small-interfering RNA (siRNA) demonstrated that IRF3 was critical for poly(I:C) and MERS-CoV induced induction of IFNβ in bat cells. Our study demonstrates that innate antiviral signaling in E. fuscus bat cells is resistant to MERS-CoV-mediated subversion. View Full-Text
Keywords: bat; IRF3; MERS-CoV; interferon bat; IRF3; MERS-CoV; interferon
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Banerjee, A.; Falzarano, D.; Rapin, N.; Lew, J.; Misra, V. Interferon Regulatory Factor 3-Mediated Signaling Limits Middle-East Respiratory Syndrome (MERS) Coronavirus Propagation in Cells from an Insectivorous Bat. Viruses 2019, 11, 152.

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