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Updated: Aug 1, 2025

Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells
Published on: June 5, 2020
In vitro cell culture models to study hepatitis B and D virus infection
Hongbo Guo1,2, Stephan Urban3,4, Wenshi Wang1,2
1Department of Pathogen Biology and Immunology; Jiangsu Key Laboratory of Immunity and Metabolism, Xuzhou Medical University, Xuzhou, China.
Insights
Developing effective hepatitis B (HBV) and hepatitis D (HDV) cures requires better in vitro models. This review details available cell culture systems crucial for studying HBV/HDV molecular biology and host interactions.
Area of Science:
- Virology
- Hepatology
- Cell Biology
Background:
- Chronic hepatitis B virus (HBV) and hepatitis D virus (HDV) infections pose a significant global health challenge.
- Current treatments manage viral replication but rarely achieve a complete cure due to persistent viral templates like cccDNA.
- Understanding virus-host interactions is crucial for developing novel curative therapies.
Purpose of the Study:
- To review and discuss available in vitro cell culture models for HBV and HDV research.
- To highlight the advantages and disadvantages of each model.
- To explore future applications of these models in advancing HBV/HDV therapies.
Main Methods:
- Review of existing literature on HBV and HDV cell culture models.
- Discussion of the role of sodium taurocholate cotransporting polypeptide (NTCP) as a key host factor.
- Analysis of viral replication and host response within different model systems.
Main Results:
- The discovery of NTCP has revolutionized HBV/HDV research, enabling new in vitro models.
- Various cell culture models now exist that support authentic HBV/HDV replication.
- Recent structural studies of human NTCP provide deeper insights into viral recognition.
Conclusions:
- Advanced cell culture models are essential for studying HBV/HDV molecular biology and host interactions.
- These models are critical for the development of new curative antiviral strategies.
- Continued development and application of these models will accelerate progress towards an HBV/HDV cure.
Abstract:
Chronic infection with the hepatitis B virus (HBV) and hepatitis D virus (HDV) can cause a major global health burden. Current medication regimens can repress viral replication and help to control disease progression, but a complete cure is hardly achieved due to the difficulties to eradicate viral templates (cccDNA and integrates). To develop novel curative antiviral therapies for HBV/HDV infection, it is vital to precisely understand the details of the molecular biology of both viruses and the virus-host interactions. One important prerequisite for gaining this aim is the availability of suitable in vitro models that support HBV/HDV infection, replicate both viruses via their authentic template and allow to adequately study host cell responses. The discovery of sodium taurocholate cotransporting polypeptide (NTCP) receptor as the most crucial host factor promoted HBV/HDV research to a new era. Recently, the structure of human NTCP was solved, gaining a deeper understanding of HBV recognition as the bona fide receptor. After decades of continuous efforts, new progress has been achieved in the development of cell culture models supporting HBV/HDV study. This review summarizes the cell culture models currently available, discusses the advantages and disadvantages of each model, and highlights their future applications in HBV and HDV research.

