Recapitulation of HDV infection in a fully permissive hepatoma cell line allows efficient drug evaluation

Hepatitis delta virus (HDV) depends on the helper function of hepatitis B virus (HBV), which provides the envelope proteins for progeny virus secretion. Current infection-competent Cell Culture models do not support assembly and secretion of HDV. By stably transducing HepG2 cells with genes encoding the NTCP-receptor and the HBV envelope proteins we produce a cell line (HepNB2.7) that allows continuous secretion of infectious progeny HDV following primary Infection. Evaluation of Antiviral drugs shows that the entry inhibitor Myrcludex B (IC₅₀: 1.4 nM) and interferon-α (IC₅₀: 28 IU/ml, but max. 60-80% inhibition) interfere with primary Infection. Lonafarnib inhibits virus secretion (IC₅₀: 36 nM) but leads to a substantial intracellular accumulation of large hepatitis delta antigen and replicative intermediates, accompanied by the induction of innate immune responses. This work provides a cell line that supports the complete HDV replication cycle and presents a convenient tool for Antiviral drug evaluation.