Effects of Overexpression of the Egyptian Fruit Bat Innate Immune Genes on Filovirus Infections in the Host Cells.

Ivan V Kuzmin,Palaniappan Ramanathan,Alexander Bukreyev,Christopher F Basler

doi:10.3389/fviro.2021.759655

Abstract

Bats constitute a large and diverse group of mammals with unique characteristics. One of these is the ability of bats to maintain various pathogens, particularly viruses, without evidence of disease. The innate immune system has been implicated as one of the important components involved in this process. However, in contrast to the human innate immune system, little data is available for bats. In the present study we generated 23 fusion constructs of innate immune genes of Egyptian fruit bat (Rousettus aegyptiacus) with mCherry as a fluorescent reporter. We evaluated the effects of overexpressing these genes on the replication of Marburg and Ebola viruses in the Egyptian fruit bat cell line R06EJ. Both viruses were substantially inhibited by overexpression of type I, II and III interferons, as well as by DDX58 (RIG-I), IFIH1, and IRF1. Our observations suggest that the broad antiviral activity of these genes reported previously in human cells is conserved in Egyptian fruit bats and these possess anti-filovirus activities that may contribute to the efficient virus clearance.

Highlights

Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, cause severe disease with high case fatality rates in humans [1]
The recombinant Marburg virus (MARV) of bat origin [38] expressing enhanced green fluorescent protein was recovered using the MARV reverse genetics systems provided by Drs Jonathan Towner, Cesar Albarino, and Stuart Nichol (CDC)
The recombinant Ebola virus (EBOV) strain Mayinga [39] expressing enhanced green fluorescent protein (eGFP) was recovered using the EBOV reverse genetics system including the full-length clone provided by Drs Jonathan Towner and Stuart Nichol and the EBOV NP, VP35, L, VP30, and T7 polymerase plasmids provided by Drs Yoshihiro Kawaoka (University of Wisconsin) and Heinz Feldmann (NIH)

Summary

Introduction

Marburg virus (MARV) and Ebola virus (EBOV), members of the family Filoviridae, cause severe disease with high case fatality rates in humans [1]. Egyptian fruit bats (Rousettus aegyptiacus) have been identified as natural reservoir hosts of MARV [2,3,4]. Several other divergent filoviruses were detected in bats of other species, including Lloviu virus [5], Reston virus [6], Bombali virus [7], Mengla virus [8]. Egyptian fruit bats survive infection with MARV and EBOV without apparent clinical signs [4, 10, 11]. Bats of other species exhibit subclinical infections and survive infections with henipaviruses and coronaviruses that cause severe diseases in humans [12,13,14]. Many factors have been suggested to play a role in the resistance to disease in bats, with major attention given to their immune system and relatively reduced inflammatory responses [15,16,17,18]

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Results

Conclusion