The bank vole (Clethrionomys glareolus)—small animal model for hepacivirus infection

Susanne Röhrs, Lineke Begeman*, Beate K. Straub, Mariana Boadella, Dennis Hanke, Kerstin Wernike, Stephan Drewes, Bernd Hoffmann, Markus Keller, Jan Felix Drexler, Christian Drosten, Dirk Höper, Thijs Kuiken, Rainer G. Ulrich, Martin Beer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Many people worldwide suffer from hepatitis C virus (HCV) infection, which is frequently persistent. The lack of efficient vaccines against HCV and the unavailability of or limited compliance with existing antiviral therapies is problematic for health care systems worldwide. Improved small animal models would support further hepacivirus research, including development of vaccines and novel antivirals. The recent discovery of several mammalian hepaciviruses may facilitate such research. In this study, we demonstrated that bank voles (Clethrionomys glareolus) were susceptible to bank vole-associated Hepacivirus F and Hepacivirus J strains, based on the detection of hepaciviral RNA in 52 of 55 experimentally inoculated voles. In contrast, interferon α/β receptor deficient C57/Bl6 mice were resistant to infection with both bank vole hepaciviruses (BvHVs). The highest viral genome loads in infected voles were detected in the liver, and viral RNA was visualized by in situ hybridization in hepatocytes, confirming a marked hepatotropism. Furthermore, liver lesions in infected voles resembled those of HCV infection in humans. In conclusion, infection with both BvHVs in their natural hosts shares striking similarities to HCV infection in humans and may represent promising small animal models for this important human disease.

Original languageEnglish
Article number2421
JournalViruses
Volume13
Issue number12
DOIs
Publication statusPublished - 3 Dec 2021

Bibliographical note

Funding Information:
The study was funded by the German Federal Ministry of Education and Research (BMBF) through the National Research Platform for Zoonoses (Network ?Rodent-borne pathogens?; project code 01KI1018 and 01KI1303 to R.G.U.), the Federal Ministry of Food and Agriculture (BMEL) through the National Research Platform for Zoonosis (28-1-91.033-14 to SR) and by the Deutsche Forschungsgemeinschaft (Priority Program ?Ecology and Species Barriers in Emerging Viral Diseases? SPP1596, UL405/1-1, to R.G.U.). The trapping of the two bank voles in Thuringia was conducted within a project commissioned and funded within the Environment Research Plan by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU; grant no. 3709 41 401; awarded to Jens Jacob, Julius K?hn-Institute). B.K.S. was funded by a grant of the DFG (STR 1160/1-2). T.K. and L.B. were funded by the EU COMPARE project (grant agreement no. 643476). Mariana Boadella was funded by a Marie Curie fellowship, ?Wild Scope? (grant no. PIEF-GA-2013-627320). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Funding Information:
Funding: The study was funded by the German Federal Ministry of Education and Research (BMBF) through the National Research Platform for Zoonoses (Network “Rodent-borne pathogens”; project code 01KI1018 and 01KI1303 to R.G.U.), the Federal Ministry of Food and Agriculture (BMEL) through the National Research Platform for Zoonosis (28-1-91.033-14 to SR) and by the Deutsche Forschungsgemeinschaft (Priority Program “Ecology and Species Barriers in Emerging Viral Diseases” SPP1596, UL405/1-1, to R.G.U.). The trapping of the two bank voles in Thuringia was conducted within a project commissioned and funded within the Environment Research Plan by the German Federal Ministry for the Environment, Nature Conservation and Nuclear Safety (BMU; grant no. 3709 41 401; awarded to Jens Jacob, Julius Kühn-Institute). B.K.S. was funded by a grant of the DFG (STR 1160/1-2). T.K. and L.B. were funded by the EU COMPARE project (grant agreement no. 643476). Mariana Boadella was funded by a Marie Curie fellowship, ‘Wild Scope’ (grant no. PIEF-GA-2013-627320). The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

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