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

Author

Listed:
  • Florian A. Lempp

    (University Hospital Heidelberg
    German Centre for Infection Research (DZIF), partner site 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
    German Centre for Infection Research (DZIF), partner site Heidelberg)

  • Stephan Urban

    (University Hospital Heidelberg
    German Centre for Infection Research (DZIF), partner site Heidelberg)

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.

Suggested Citation

  • Florian A. Lempp & Franziska Schlund & Lisa Rieble & Lea Nussbaum & Corinna Link & Zhenfeng Zhang & Yi Ni & Stephan Urban, 2019. "Recapitulation of HDV infection in a fully permissive hepatoma cell line allows efficient drug evaluation," Nature Communications, Nature, vol. 10(1), pages 1-11, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-10211-2
    DOI: 10.1038/s41467-019-10211-2
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