Next Article in Journal
Geographical Variability Affects CCHFV Detection by RT–PCR: A Tool for In-Silico Evaluation of Molecular Assays
Previous Article in Journal
Look Who’s Talking: T-Even Phage Lysis Inhibition, the Granddaddy of Virus-Virus Intercellular Communication Research
Open AccessArticle

An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV

1
Department of Biochemistry, Faculty of Pharmacy, Mahidol University, Bangkok 10400, Thailand
2
Excellent Center for Drug Discovery, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
3
Department of Biotechnology, Faculty of Science, Mahidol University, Bangkok 10400, Thailand
4
Department of Pharmacology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand
5
Department of Pediatrics, Faculty of Medicine Ramathibodi Hospital, Mahidol University, Bangkok 10400, Thailand
*
Authors to whom correspondence should be addressed.
Viruses 2019, 11(10), 952; https://doi.org/10.3390/v11100952
Received: 10 September 2019 / Revised: 14 October 2019 / Accepted: 15 October 2019 / Published: 16 October 2019
(This article belongs to the Section Animal Viruses)
More than 350 million people worldwide have been persistently infected with the hepatitis B virus (HBV). Chronic HBV infection could advance toward liver cirrhosis and hepatocellular carcinoma. The intervention with prophylactic vaccine and conventional treatment could suppress HBV, but could not completely eradicate it. The major obstacle for investigating curative antiviral drugs are the incompetence of hepatocyte models that should have closely imitated natural human infection. Here, we demonstrated that an immortalized hepatocyte-like cell line (imHC) could accommodate for over 30 days the entire life cycle of HBV prepared from either established cultured cells or clinically-derived fresh isolates. Normally, imHCs had intact interferon signaling with anti-viral action. Infected imHCs responded to treatments with direct-acting antiviral drugs (DAAs) and interferons (IFNs) by diminishing HBV DNA, the covalently closed circular DNA (cccDNA) surface antigen of HBV (HBsAg, aka the Australia antigen) and the hepatitis B viral protein (HBeAg). Notably, we could observe and quantify HBV spreading from infected cells to naïve cells using an imHC co-culture model. In summary, this study constructed a convenient HBV culture model that allows the screening for novel anti-HBV agents with versatile targets, either HBV entry, replication or cccDNA formation. Combinations of agents aiming at different targets should achieve a complete HBV eradication. View Full-Text
Keywords: hepatitis B; viral spreading; cccDNA; hepatocyte; NTCP; HBV; cell culture hepatitis B; viral spreading; cccDNA; hepatocyte; NTCP; HBV; cell culture
Show Figures

Figure 1

MDPI and ACS Style

Sa-ngiamsuntorn, K.; Thongsri, P.; Pewkliang, Y.; Wongkajornsilp, A.; Kongsomboonchoke, P.; Suthivanich, P.; Borwornpinyo, S.; Hongeng, S. An Immortalized Hepatocyte-Like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV. Viruses 2019, 11, 952.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop