An evolutionary divergent pestivirus lacking the N^pro gene systemically infects a whale species

ABSTRACT

Pestiviruses typically infect members of the order Artiodactyla, including ruminants and pigs, although putative rat and bat pestiviruses have also been described. In the present study, we identified and characterized an evolutionary divergent pestivirus in the toothed whale species, harbour porpoise (Phocoena phocoena). We tentatively named the virus Phocoena pestivirus (PhoPeV). PhoPeV displays a typical pestivirus genome organization except for the unique absence of N^pro, an N-terminal autoprotease that targets the innate host immune response. Evolutionary evidence indicates that PhoPeV emerged following an interspecies transmission event from an ancestral pestivirus that expressed N^pro. We show that 9% (n = 10) of stranded porpoises from the Dutch North Sea coast (n = 112) were positive for PhoPeV and they displayed a systemic infection reminiscent of non-cytopathogenic persistent pestivirus infection. The identification of PhoPeV extends the host range of pestiviruses to cetaceans (dolphins, whales, porpoises), which are considered to have evolved from artiodactyls (even-toed ungulates). Elucidation of the pathophysiology of PhoPeV infection and N^pro unique absence will add to our understanding of molecular mechanisms governing pestivirus pathogenesis.

KEYWORDS:

• Pestivirus
• porpoise
• systemic
• marine mammal
• N^pro

Acknowledgements

We wish to thank Ilka Baumann for technical assistance and the NGS core facility at the Hannover Medical School, Germany, for operation of the Illumina MiSeq system. We also thank SOS Dolfijn for their assistance and support in kind. A.O., T.K., C.E. and M.L. designed the study. C.E. and T.K. performed autopsies and collected tissue samples as part of regional stranding networks. W.K.J., M.v.d.B., P.v.R, M.P., I.B., S.J., T.K. and K.J. performed the laboratory work and data interpretation. W.K.J., M.L., T.K. and A.O. wrote the manuscript. All authors commented on and approved the manuscript.

Disclosure statement

No potential conflict of interest was reported by the authors.

Data availability

The sequences generated in this study from two full-length PhoPeV genomes have been deposited under GenBank accession numbers (MK910227-37). Other data are available upon request.

Additional information

Funding

This work was supported by the grant from the Niedersachsen-Research Network on Neuroinfectiology 2 (N-RENNT-2) from the Ministry of Science and Culture of Lower Saxony, Germany; R2N Project funded by the Federal State of Lower Saxony, Germany; and the European Union’s Horizon 2020 [grant number 643476] “COMPARE”.