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Modeling Hepatitis B Virus Infection in Non-Hepatic 293T-NE-3NRs Cells
Published on: June 5, 2020
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Cell Culture Models and Animal Models for HBV Study
Feng Li1,2, Zhuo Wang3, Fengyu Hu4
1Lineberger Comprehensive Cancer Center, Department of Microbiology and Immunology, School of Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC, USA. gz8h_lifeng@126.com.
Advances in Experimental Medicine and Biology
|November 20, 2019
Summary
Developing effective Hepatitis B virus (HBV) treatments requires advanced cell and animal models. This review details the evolution and protocols for HBV models, aiding research into viral lifecycle and host interactions.
Area of Science:
- Hepatology and Virology
- Infectious Diseases Research
- Biomedical Model Development
Background:
- Hepatitis B virus (HBV) research necessitates representative cell and animal models for studying its lifecycle, viral-host interactions, and antiviral therapies.
- Over 40 years, HBV models have advanced from non-infectious cell cultures (e.g., HepG2.2.15, HepAD38) to infection models, with HepaRG cells historically dominant but complex.
- The discovery of sodium-taurocholate cotransporting polypeptide (NTCP) as the HBV receptor revolutionized infection models, while recombinant cccDNA (rc-cccDNA) offers a new avenue for eradication studies.
Purpose of the Study:
- To provide a historical overview of the evolution of cell and animal models for Hepatitis B virus (HBV) research.
- To summarize the advantages and disadvantages of various HBV models, including cell culture and animal systems.
- To present protocols for key HBV infection and replication models, facilitating future research.
Main Methods:
- Review of historical advancements in HBV cell culture models, including plasmid DNA transfection, integrated cell lines, and drug-regulated production systems.
- Analysis of HBV infection models, highlighting the impact of NTCP receptor identification and the development of rc-cccDNA transfection methods.
- Examination of HBV animal models, from early transgenic mice to non-integrated and humanized liver models, discussing their limitations and applications.
Main Results:
- HBV cell culture models have progressed from basic transfection systems to sophisticated drug-regulated and infection-competent cells (e.g., HepG2-NTCP).
- Animal models have evolved to better represent HBV infection, with humanized liver models currently supporting the complete HBV lifecycle in vivo, despite high costs.
- Various methods have been developed to enable HBV cccDNA formation and persistence in experimental systems.
Conclusions:
- The development of HBV models has significantly improved over decades, offering diverse tools for scientific inquiry.
- HepG2-NTCP cells and humanized mouse models represent significant advancements for studying HBV infection and evaluating therapies.
- Protocols for HepG2-NTCP cell infection, HepG2 rc-cccDNA transfection, and NRG-Fah-/- liver humanized mouse infection are provided to aid researchers.
