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Journal Articles Antiviral Research Year : 2023

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


Chronic hepatitis D is the most aggressive form of chronic viral hepatitis. It is caused by superinfection 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 of viral particles infectivity. We confirmed interaction of HDV proteins with a previously described host factor in HuH7-2C8D cells and additionally showed that these cells are suitable for coculture 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, host interactions. HuH7-2C8D cells are also suitable for high-throughput antivirals screening assays for the development of new therapeutic strategies.
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Dates and versions

hal-03883116 , version 1 (02-12-2022)



Charlotte Bach, Julie Lucifora, Marion Delphin, Laura Heydmann, Margaux Heuschkel, et al.. A stable hepatitis D virus-producing cell line for host target and drug discovery. Antiviral Research, 2023, 209, pp.105477. ⟨10.1016/j.antiviral.2022.105477⟩. ⟨hal-03883116⟩
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