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J Virol. 2018 Dec 19. pii: JVI.01404-18. doi: 10.1128/JVI.01404-18. [Epub ahead of print]

Koala and wombat gammaherpesviruses encode the first known viral nucleoside triphosphate diphosphohydrolase (NTPDase) homologs and are phylogenetically divergent from all known gammaherpesviruses.

Author information

1
Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Building 400, Parkville, 3052. VIC, Australia pvaz@unimelb.edu.au.
2
Asia-Pacific Centre for Animal Health, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Building 400, Parkville, 3052. VIC, Australia.
3
PharmaCenter Bonn, Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, D-53121 Bonn, Germany.
4
CSIRO Manufacturing, Parkville, Victoria, Australia.

Abstract

There is a large taxonomic gap in our understanding of mammalian herpesvirus genetics and evolution corresponding to those herpesviruses that infect marsupials, which diverged from eutherian mammals approximately 150 million years ago (mya). We compare the genomes of two marsupial gammaherpesviruses; Phascolarctid gammaherpesvirus 1 (PhaHV1) and Vombatid gammaherpesvirus 1 (VoHV1), which infect koalas (Phascolartos cinereus) and wombats (Vombatus ursinus), respectively. The core viral genomes were approximately 117 kbp and 110 kbp in length, respectively, sharing 69% nucleotide sequence pair-wise identity. Phylogenetic analyses showed that PhaHV1 and VoHV1 formed a separate branch and may indicate a new gammaherpesvirus genus. The genomes contained 60 predicted ORFs homologous to those in eutherian herpesviruses, and 20 ORFs not yet found in any other herpesvirus. Seven of these ORFs were shared by the two viruses, indicating that they were probably acquired pre-speciation, approximately 30-40 mya. One of these shared genes encodes a putative nucleoside triphosphate diphosphohydrolase (NTPDase). NTPDases are usually found in mammals and higher order eukaryotes, with a very small number found in bacteria. This is the first time an NTPDase has been identified in any viral genome. Interrogation of public transcriptomic datasets from two koalas identified PhaHV1-specific transcripts in multiple host tissues, including transcripts for the novel NTPDase. PhaHV1 ATPase activity was also demonstrated in vitro, suggesting that the encoded NTPDase is functional during viral infection. In mammals, NTPDases are important in downregulation of the inflammatory and immune responses, but the role of the PhaHV1 NTPDase during viral infection remains to be determined.IMPORTANCE: The genome sequences of the koala and wombat gammaherpesviruses show that the viruses form a distinct branch, indicative of a novel genus within the Gammaherpesvirinae Their genomes contain several new ORFs, including ORFs encoding an ST6Gal that is phylogenetically closest to poxvirus and insect homologs, and the first reported viral NTPDase. NTPDases are ubiquitously expressed in mammals, and are also present in several parasitic, fungal and bacterial pathogens. In mammals, these cell-surface localized NTPDases play essential roles in thromboregulation, inflammation and immune suppression. In this study, we demonstrate that the virus-encoded NTPDase is enzymatically active and is transcribed during natural infection of the host. Understanding how these enzymes benefit viruses can help to inform how they may cause disease or evade host immune defenses.

PMID:
30567986
DOI:
10.1128/JVI.01404-18

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