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

Florian A. Lempp, Franziska Schlund, Lisa Rieble, Lea Nussbaum, Corinna Link, Zhenfeng Zhang, Yi Ni and Stephan Urban ()
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Florian A. Lempp: University Hospital Heidelberg
Franziska Schlund: University Hospital Heidelberg
Lisa Rieble: University Hospital Heidelberg
Lea Nussbaum: University Hospital Heidelberg
Corinna Link: University Hospital Heidelberg
Zhenfeng Zhang: University Hospital Heidelberg
Yi Ni: University Hospital Heidelberg
Stephan Urban: University Hospital Heidelberg

Nature Communications, 2019, vol. 10, issue 1, 1-11

Abstract: Abstract 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.

Date: 2019
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DOI: 10.1038/s41467-019-10211-2

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