Ribavirin Inhibits Parrot Bornavirus 4 Replication in Cell Culture.

Jeffrey M. B. Musser,J. Jill Heatley,Paulina Escandon,Ian R. Tizard,Paulette F. Suchodolski,Anastasia V. Koinis,Jianhua Guo,Kylene Kehn-Hall

doi:10.1371/journal.pone.0134080

Jeffrey M. B. Musser, J. Jill Heatley + Show 6 more

Open Access

https://doi.org/10.1371/journal.pone.0134080

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Journal: PloS one	Publication Date: Jul 29, 2015
Citations: 23	License type: CC BY 4.0

Affiliation: Texas A&M University, Morris Animal Foundation

Abstract

Parrot bornavirus 4 is an etiological agent of proventricular dilatation disease, a fatal neurologic and gastrointestinal disease of psittacines and other birds. We tested the ability of ribavirin, an antiviral nucleoside analog with antiviral activity against a range of RNA and DNA viruses, to inhibit parrot bornavirus 4 replication in duck embryonic fibroblast cells. Two analytical methods that evaluate different products of viral replication, indirect immunocytochemistry for viral specific nucleoprotein and qRT-PCR for viral specific phosphoprotein gene mRNA, were used. Ribavirin at concentrations between 2.5 and 25 μg/mL inhibited parrot bornavirus 4 replication, decreasing viral mRNA and viral protein load, in infected duck embryonic fibroblast cells. The addition of guanosine diminished the antiviral activity of ribavirin suggesting that one possible mechanism of action against parrot bornavirus 4 may likely be through inosine monophosphate dehydrogenase inhibition. This study demonstrates parrot bornavirus 4 susceptibility to ribavirin in cell culture.

Highlights

Parrot bornavirus 4 (PaBV-4) is an enveloped, non-segmented, negative sense RNA virus in the family Bornaviridae
Our results demonstrated that ribavirin decreased viral protein and mRNA expression in PaBV-4 infected cell cultures
To ascertain that the cells were not contaminated with any virus of the species Psittaciform 1 bornavirus, an aliquot of the stored duck embryonic fibroblast (DEF) cells was assayed by reverse transcription (RT)-PCR [29]

Summary

Introduction

Parrot bornavirus 4 (PaBV-4) is an enveloped, non-segmented, negative sense RNA virus in the family Bornaviridae. Recent phylogenetic analysis of viruses within the family Bornaviridae, which includes the formerly named Avian Bornavirus, resulted in new nomenclature and taxonomic reorganization of Bornaviridae into 5 species: Mammalian 1 bornavirus, Psittaciform 1 bornavirus, Passeriform 1 bornavirus, Passeriform 2 bornavirus, and Waterbird 1 bornavirus [1]. Epidemiological and experimental results support that PaBV-1, -2, -3, -4, -7, all members of the species Psittaciform 1 bornavirus, are etiological agents of proventricular dilatation disease (PDD), a fatal neurologic and gastrointestinal syndrome of psittacines and other birds [2,3,4]. Bornaviruses are noncytopathic in cell culture [4,9].

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