Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses

Egi Kardia, Omid Fakhri, Megan Pavy, Hugh Mason, Nina Huang, Elena Smertina, Maria Jenckel, Nias Y G Peng, Mary K Estes, Tanja Strive, Michael Frese, Ina Smith, Robyn Hall

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)

Abstract

The genus Lagovirus of the family Caliciviridae contains some of the most virulent vertebrate viruses known. Lagoviruses infect leporids, such as rabbits, hares and cottontails. Highly pathogenic viruses such as Rabbit haemorrhagic disease virus 1 (RHDV1) cause a fulminant hepatitis that typically leads to disseminated intravascular coagulation within 24-72 h of infection, killing over 95 % of susceptible animals. Research into the pathophysiological mechanisms that are responsible for this extreme phenotype has been hampered by the lack of a reliable culture system. Here, we report on a new ex vivo model for the cultivation of lagoviruses in cells derived from the European rabbit (Oryctolagus cuniculus) and European brown hare (Lepus europaeus). We show that three different lagoviruses, RHDV1, RHDV2 and RHDVa-K5, replicate in monolayer cultures derived from rabbit hepatobiliary organoids, but not in monolayer cultures derived from cat (Felis catus) or mouse (Mus musculus) organoids. Virus multiplication was demonstrated by (i) an increase in viral RNA levels, (ii) the accumulation of dsRNA viral replication intermediates and (iii) the expression of viral structural and non-structural proteins. The establishment of an organoid culture system for lagoviruses will facilitate studies with considerable implications for the conservation of endangered leporid species in Europe and North America, and the biocontrol of overabundant rabbit populations in Australia and New Zealand.
Original languageEnglish
Article number001874
Pages (from-to)1-31
Number of pages31
JournalJournal of General Virology
Volume104
Issue number8
DOIs
Publication statusPublished - Aug 2023

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