Hepatology International

, Volume 10, Issue 4, pp 559–566

HBV culture and infectious systems

Review Article

DOI: 10.1007/s12072-016-9712-y

Cite this article as:
Hayes, C.N. & Chayama, K. Hepatol Int (2016) 10: 559. doi:10.1007/s12072-016-9712-y


While an effective vaccine against hepatitis B virus (HBV) has long been available, chronic HBV infection remains a severe global public health concern. Current treatment options have limited effectiveness, and long-term therapy is required to suppress HBV replication; however, complete elimination of the virus is rare. The lack of suitable animal models and infection systems has hindered efforts to unravel the HBV life cycle, particularly the early events in HBV entry, which appear to be highly species- and tissue-specific. Human primary hepatocytes remain the gold standard for HBV replication studies but are limited by availability and variability. While the HepaRG cell line is permissive for HBV replication, other hepatoma cell lines such as HepG2 do not support HBV replication. The recent discovery of sodium taurocholate transporting peptide (NTCP) as a primary receptor for HBV binding has led to the development of replication-competent cell lines such as HepG2–NTCP. Human hepatocytes grown in chimeric mice have provided another approach that allows primary human hepatocytes to be used while overcoming many of their limitations. Although the difficulty in developing HBV infection systems has hindered development of effective treatments, the variability and limited replication efficiency among cell lines point to additional liver-specific factors involved in HBV infection. It is hoped that HBV infection studies will lead to novel drug targets and therapeutic options for the treatment of chronic HBV infection.


Hepatitis B virus HepaRG HepG2 NTCP Human hepatocyte chimeric mice 



Covalently closed circular DNA


Dimethyl sulfoxide


Hepatitis B virus


Sodium taurocholate transporting peptide

Copyright information

© Asian Pacific Association for the Study of the Liver 2016

Authors and Affiliations

  1. 1.Department of Gastroenterology and Metabolism, Applied Life Sciences, Institute of Biomedical and Health SciencesHiroshima UniversityHiroshimaJapan
  2. 2.Liver Research Project CenterHiroshima UniversityHiroshimaJapan
  3. 3.Laboratory for Digestive DiseasesCenter for Genomic Medicine, RIKENHiroshimaJapan

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