Abstract

The Egyptian rousette bat (ERB) is the only known Marburg virus (MARV) reservoir host. ERBs develop a productive MARV infection with low viremia and shedding but no overt disease, suggesting this virus is efficiently controlled by ERB antiviral responses. This dynamic would contrast with humans, where MARV-mediated interferon (IFN) antagonism early in infection is thought to contribute to the severe, often fatal disease. The newly-annotated ERB genome and transcriptome have now enabled us to use a custom-designed NanoString nCounter ERB CodeSet in conjunction with RNA-seq to investigate responses in a MARV-infected ERB cell line. Both transcriptomic platforms correlated well and showed that MARV inhibited the antiviral program in ERB cells, while an IFN antagonism-impaired MARV was less efficient at suppressing the response gene induction, phenotypes previously reported for primate cells. Interestingly, and despite the expansion of IFN loci in the ERB genome, neither MARV showed specific induction of almost any IFN gene. However, we detected an upregulation of putative, unannotated ERB antiviral paralogs, as well as an elevated basal expression in uninfected ERB cells of key antiviral genes.

Highlights

  • Bats are the second-largest order of mammals on Earth and inhabit diverse biotopes worldwide.In recent years, many bat species have been recognized as reservoir hosts for a wide array of viruses [1,2]

  • We conducted a transcriptomic analysis of an Egyptian rousette bat (ERB) kidney-derived cell line (RoNi) infected with a recombinant Marburg virus (MARV) derived from a wild-caught ERB isolate [24]

  • We find that MARV WT infections strongly suppresses antiviral responses in RoNi cells, while infection with IFN antagonism-deficient MARV VP35mut results in a significant antiviral gene expression

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Summary

Introduction

Many bat species have been recognized as reservoir hosts for a wide array of viruses [1,2]. Contact between infected bats and other animals occasionally produces spillover zoonoses that can be highly pathogenic. Among the most notorious emerging pathogens linked to bats are filoviruses, including Marburg virus (MARV) and Ebola virus (EBOV) [3]. Both viruses cause severe diseases in humans and non-human primates (NHPs) with high case fatality rates [4]. Ecological and laboratory efforts have identified the Egyptian rousette bat (Rousettus aegyptiacus, ERB) as a natural reservoir for Marburg viruses [5,6,7].

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