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

  • Nat Commun. 2019 May 22;10(1):2265. doi: 10.1038/s41467-019-10211-2.
Florian A Lempp  1  2 ,  Franziska Schlund  1 ,  Lisa Rieble  1 ,  Lea Nussbaum  1 ,  Corinna Link  1 ,  Zhenfeng Zhang  1 ,  Yi Ni  1  2 ,  Stephan Urban  3  4
Affiliations
  • 1. Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, 69120, Germany.
  • 2. German Centre for Infection Research (DZIF), partner site Heidelberg, Heidelberg, 69120, Germany.
  • 3. Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, 69120, Germany. [email protected].
  • 4. German Centre for Infection Research (DZIF), partner site Heidelberg, Heidelberg, 69120, Germany. [email protected].
PMID: 31118422 DOI: 10.1038/s41467-019-10211-2
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.

Products