A stable hepatitis D virus-producing cell line for host target and drug discovery

Autor: Charlotte Bach, Julie Lucifora, Marion Delphin, Laura Heydmann, Margaux J. Heuschkel, Caroline Pons, Kaku Goto, Els Scheers, Catherine Schuster, David Durantel, Frederik Pauwels, Thomas F. Baumert, Eloi R. Verrier
Přispěvatelé: Institut de Recherche sur les Maladies Virales et Hépatiques (IVH), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), This work of the Interdisciplinary Thematic Institute IMCBio, as part of the ITI 2021-2028 program of the University of Strasbourg, CNRS and Inserm, was supported by IdEx Unistra (ANR-10IDEX-0002), and by SFRI-STRAT’US project (ANR 20-SFRI-0012) and EUR IMCBio (ANR-17-EURE0023) under the framework of the French Investments for the Future Program. E.R.V acknowledges fundings from Inserm, the Agence Nationale de Recherches sur le Sida et les Hépatites Virales (ANRS, grant number ECTZ171594), and the French National Research Agency (ANR, grant number ANR-21CE15-0035-01 DELTArget). J.L. acknowledges fundings from Inserm, CNRS, University of Lyon, and ANRS (grant number ECTZ172540). T. F. B and E. R. V. received funding from Janssen Pharmaceutica as part of the VLAIO project ABDeCo (HBC.2017.0895). T. F. B acknowledges funding from the European Union (EU ERC-AdG-2014-HEPCIR #671231 and ARC TheraHCC2.0 IHU201901299, European Project: 671231,H2020,ERC-2014-ADG,HEPCIR(2016)
Rok vydání: 2022
Předmět:
Zdroj: Antiviral Research
Antiviral Research, 2023, 209, pp.105477. ⟨10.1016/j.antiviral.2022.105477⟩
ISSN: 1872-9096
0166-3542
Popis: Chronic hepatitis D is the most aggressive form of chronic viral hepatitis. It is caused by super-infection of hepatitis B virus (HBV)-infected hepatocytes with hepatitis D virus (HDV). While the recent conditional approval of bulevirtide for HDV treatment offers a new therapeutic modality in Europe, there is an unmet medical need to further improve therapy. A more detailed characterization of virus-host interactions is needed for the identification of novel therapeutic targets. Addressing this need, we engineered a new stably-transformed cell line, named HuH7-2C8D, producing high titer recombinant HDV and allowing the study of viral particles morphogenesis and infectivity. Using this culture system, where viral propagation by re-infection is limited, we observed an increased accumulation of edited version of the viral genomes within secreted HDV viral particles over time that is accompanied with a decrease in viral particle infectivity. We confirmed the interaction of HDV proteins with a previously described host factor in HuH7-2C8D cells and additionally showed that these cells are suitable for co-culture assays with other cell types such as macrophages. Finally, the use of HuH7-2C8D cells allowed to confirm the dual antiviral activity of farnesyl transferase inhibitors, including the clinical candidate lonafarnib, against HDV. In conclusion, we have established an easy-to-handle cell culture model to investigate HDV replication, morphogenesis, and host interactions. HuH7-2C8D cells are also suitable for high-throughput antiviral screening assays for the development of new therapeutic strategies. journal article research support, non-u.s. gov't 2023 Jan 2022 11 26 imported
Databáze: OpenAIRE
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