Novel hepaci- and pegi-like viruses in native Australian wildlife and non-human primates.

John H -O Pettersson,Craig Moritz,Erin Harvey,Jan Buchmann,Edward C Holmes,Karrie Rose,Mang Shi,Ashleigh F Porter,Wei-Shan Chang,John-Sebastian Eden

doi:10.1093/ve/veaa064

Abstract

The Flaviviridae family of positive-sense RNA viruses contains important pathogens of humans and other animals, including Zika virus, dengue virus, and hepatitis C virus. The Flaviviridae are currently divided into four genera—Hepacivirus, Pegivirus, Pestivirus, and Flavivirus—each with a diverse host range. Members of the genus Hepacivirus are associated with an array of animal species, including humans, non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa, also including humans. Using a combination of total RNA and whole-genome sequencing we identified four novel hepaci-like viruses and one novel variant of a known hepacivirus in five species of Australian wildlife. The hosts infected comprised native Australian marsupials and birds, as well as a native gecko (Gehyra lauta). From these data we identified a distinct marsupial clade of hepaci-like viruses that also included an engorged Ixodes holocyclus tick collected while feeding on Australian long-nosed bandicoots (Perameles nasuta). Distinct lineages of hepaci-like viruses associated with geckos and birds were also identified. By mining the SRA database we similarly identified three new hepaci-like viruses from avian and primate hosts, as well as two novel pegi-like viruses associated with primates. The phylogenetic history of the hepaci- and pegi-like viruses as a whole, combined with co-phylogenetic analysis, provided support for virus-host co-divergence over the course of vertebrate evolution, although with frequent cross-species virus transmission. Overall, our work highlights the diversity of the Hepacivirus and Pegivirus genera as well as the uncertain phylogenetic distinction between.

Highlights

As the vast majority of emerging infectious disease in humans are caused by viral zoonoses (Jones et al 2008), the characterisation of animal viruses is critical for identifying potential disease reservoirs and providing models for the study of human viruses (Pfaender et al 2014, 2015)
Members of the genus Hepacivirus are associated with an array of animal species, including humans, non-human primates, other mammalian species, as well as birds and fish, while the closely related pegiviruses have been identified in a variety of mammalian taxa, including humans
To identify hepaci- and pegi-like viruses present in the sequence read archive (SRA), we screened primates, birds and marsupials. We focused on these taxonomic groups because 1, hepatitis C virus (HCV) is clearly a human virus it is uncertain whether it is present in non-human primates, 2, a number of novel hepaci- and pegi-like viruses have recently been identified in avian hosts suggesting that these might be a rich source of novel viruses, and 3, to confirm the presence of a marsupial specific-lineage as suggested by our previous studies

Summary

Introduction

As the vast majority of emerging infectious disease in humans are caused by viral zoonoses (Jones et al 2008), the characterisation of animal viruses is critical for identifying potential disease reservoirs and providing models for the study of human viruses (Pfaender et al 2014, 2015). Two related groups of viruses that have repeated emerged in new hosts are the genera Hepacivirus and Pegivirus from the family Flaviviridae of single-strand positive-sense RNA viruses. Two hepaci-like virus sequences have been identified in arthropods (a mosquito and tick), their true host is uncertain (Harvey et al 2019a; Williams et al 2020). Despite such host diversity, hepaciviruses remain synonymous with liver infection, with the most notable example being human hepatitis C virus (HCV). While some non-primate hepaci-like viruses have been well characterised, equine hepacivirus ( known as hepacivirus AK, or non-primate hepacivirus) and canine hepacivirus (CHV), it seems likely that HCV arose from a currently unknown zoonotic source (Pybus and Gray 2013; Lyons et al 2014; Thezeet al. 2015; Hartlage, Cullen, and Kapoor 2016)

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Conclusion