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

Arinjay Banerjee,Noreen Rapin,Vikram Misra,Darryl Falzarano,Jocelyne Lew

doi:10.3390/v11020152

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.

Highlights

Bats are ecologically important mammals that are speculated to be reservoirs of several emerging viruses, including coronaviruses [1,2]
We observed that Middle-East respiratory syndrome (MERS)-CoV propagated to significantly higher titers in human cells than big brown bat cells that were infected with either a low (Figure 1A) or high (Figure 1B) multiplicity of infection (MOI)
While virus yields from the three permissive human cell lines varied, they were still higher than the yield from bat Efk3 cells

Summary

Introduction

Bats are ecologically important mammals that are speculated to be reservoirs of several emerging viruses, including coronaviruses [1,2]. Over nine hundred coronavirus sequences from bats have been reported [4] and recently, coronaviruses thought to have spilled-over from bats have caused serious disease in humans and agricultural animals. These include severe acute respiratory syndrome (SARS)-CoV, Middle-East respiratory syndrome (MERS)-CoV, porcine epidemic diarrhea virus (PEDV), and swine acute diarrhea syndrome (SADS) coronavirus [5,6,7,8,9,10,11,12]. The spill-over of these viruses to susceptible hosts, including humans and agricultural animals, often results in severe disease.

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Conclusion