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

https://www.ncbi.nlm.nih.gov/pubmed/36511319

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.