A stable hepatitis D virus-producing cell line for host target and drug discovery.
Fiche publication
Date publication
novembre 2022
Journal
Antiviral research
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BAUMERT Thomas, Dr VERRIER Eloi
Tous les auteurs :
Bach C, Lucifora J, Delphin M, Heydmann L, Heuschkel MJ, Pons C, Goto K, Scheers E, Schuster C, Durantel D, Pauwels F, Baumert TF, Verrier ER
Lien Pubmed
Résumé
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.
Mots clés
Cell culture model, Hepatitis D virus, Lonafarnib, Virus-host interactions
Référence
Antiviral Res. 2022 11 26;209:105477