1887

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Volume 104, Issue 8

Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses Open Access

Abstract

The genus of the family contains some of the most virulent vertebrate viruses known. Lagoviruses infect leporids, such as rabbits, hares and cottontails. Highly pathogenic viruses such as (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 model for the cultivation of lagoviruses in cells derived from the European rabbit () and European brown hare (). 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 () or mouse () 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.

  • Received:
  • Accepted:
  • Published Online:
Keyword(s): cell culture model , ex vivo , lagovirus , organoids , Oryctolagus cuniculus , rabbit and RHDV
Funding
This study was supported by the:
  • Commonwealth Scientific and Industrial Research Organisation
    • Principle Award Recipient: RobynN Hall
  • Meat and Livestock Australia (Award P.PSH.1059)
    • Principle Award Recipient: RobynN Hall
© 2023 Crown copyright
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License. This article was made open access via a Publish and Read agreement between the Microbiology Society and the corresponding author’s institution.
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2023-08-16
2024-04-27
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Hepatobiliary organoids derived from leporids support the replication of hepatotropic lagoviruses
J. Gen. Virol. 104, 001874 (2023); https://doi.org/10.1099/jgv.0.001874
/content/journal/jgv/10.1099/jgv.0.001874
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