Recapitulation of HDV infection in a fully permissive hepatoma cell line allows efficient drug evaluation.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 31118422.
- Also identified by DOI 10.1038/s41467-019-10211-2 and PMC identifier 6531471.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
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 (IC<sub>50</sub>: 1.4 nM) and interferon-α (IC<sub>50</sub>: 28 IU/ml, but max. 60-80% inhibition) interfere with primary infection. Lonafarnib inhibits virus secretion (IC<sub>50</sub>: 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.
Medical subject headings
- Antiviral Agents
- Hepatitis Delta Virus
- Viral Envelope Proteins
- Virus Replication