Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Sep 20;8(9):261.
doi: 10.3390/v8090261.

Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection

Eloi R Verrier  1   2 , Che C Colpitts  3   4 , Catherine Schuster  5   6 , Mirjam B Zeisel  7   8 , Thomas F Baumert  9   10   11
Affiliations
Review

Cell Culture Models for the Investigation of Hepatitis B and D Virus Infection

Eloi R Verrier et al. Viruses. .

Abstract

Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections are major causes of liver disease and hepatocellular carcinoma worldwide. Despite the presence of an efficient preventive vaccine, more than 250 million patients are chronically infected with HBV. Current antivirals effectively control but only rarely cure chronic infection. While the molecular biology of the two viruses has been characterized in great detail, the absence of robust cell culture models for HBV and/or HDV infection has limited the investigation of virus-host interactions. Native hepatoma cell lines do not allow viral infection, and the culture of primary hepatocytes, the natural host cell for the viruses, implies a series of constraints restricting the possibilities of analyzing virus-host interactions. Recently, the discovery of the sodium taurocholate co-transporting polypeptide (NTCP) as a key HBV/HDV cell entry factor has opened the door to a new era of investigation, as NTCP-overexpressing hepatoma cells acquire susceptibility to HBV and HDV infections. In this review, we summarize the major cell culture models for HBV and HDV infection, discuss their advantages and limitations and highlight perspectives for future developments.

Keywords: NTCP; Viral cell entry; hepatocytes; hepatoma cells; life cycle.

PubMed Disclaimer

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Schematic representation of the HBV and HDV life cycles in hepatocytes. HBV: hepatitis B virus; HDV: hepatitis D virus; HDV RNP: HDV ribonucleoprotein. HBV NC: HBV nucleocapsid. rcDNA: relaxed circular DNA. −/+ssRNA: negative/positive single-stranded RNA. cccDNA: covalently closed circular DNA. HBV pgRNA: HBV pregenomic RNA. HDAgs: hepatitis D antigens. HBcAg: HBV core antigen. HBsAg: HBV surface antigen. p: HBV polymerase. HBV SVP: HBV subviral particle. TDP2: tyrosyl-DNA phosphodiesterase 2.
See this image and copyright information in PMC

References

    1. Rehermann B., Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat. Rev. Immunol. 2005;5:215–229. doi: 10.1038/nri1573. - DOI - PubMed
    1. El-Serag H.B. Epidemiology of viral hepatitis and hepatocellular carcinoma. Gastroenterology. 2012;142:1264–1273e1. doi: 10.1053/j.gastro.2011.12.061. - DOI - PMC - PubMed
    1. Thomas D., Zoulim F. New challenges in viral hepatitis. Gut. 2012;61(Suppl. S1):i1–i5. doi: 10.1136/gutjnl-2012-302122. - DOI - PubMed
    1. Zeisel M.B., Lucifora J., Mason W.S., Sureau C., Beck J., Levrero M., Kann M., Knolle P.A., Benkirane M., Durantel D., et al. Towards an HBV cure: State-of-the-art and unresolved questions-report of the ANRS workshop on HBV cure. Gut. 2015;64:1314–1326. doi: 10.1136/gutjnl-2014-308943. - DOI - PubMed
    1. Habersetzer F., Moenne-Loccoz R., Meyer N., Schvoerer E., Simo-Noumbissie P., Dritsas S., Baumert T.F., Doffoel M. Loss of hepatitis B surface antigen in a real-life clinical cohort of patients with chronic hepatitis B virus infection. Liver Int. 2015;35:130–139. doi: 10.1111/liv.12661. - DOI - PubMed