In Vitro Systems for Studying Different Genotypes/Sub-Genotypes of Hepatitis B Virus: Strengths and Limitations
Open Access
- 22 March 2020
- Vol. 12 (3), 353
- https://doi.org/10.3390/v12030353
Abstract
Hepatitis B virus (HBV) infects the liver resulting in end stage liver disease, cirrhosis, and hepatocellular carcinoma. Despite an effective vaccine, HBV poses a serious health problem globally, accounting for 257 million chronic carriers. Unique features of HBV, including its narrow virus–host range and its hepatocyte tropism, have led to major challenges in the development of suitable in vivo and in vitro model systems to recapitulate the HBV replication cycle and to test various antiviral strategies. Moreover, HBV is classified into at least nine genotypes and 35 sub-genotypes with distinct geographical distributions and prevalence, which have different natural histories of infection, clinical manifestation, and response to current antiviral agents. Here, we review various in vitro systems used to study the molecular biology of the different (sub)genotypes of HBV and their response to antiviral agents, and we discuss their strengths and limitations. Despite the advances made, no system is ideal for pan-genotypic HBV research or drug development and therefore further improvement is required. It is necessary to establish a centralized repository of HBV-related generated materials, which are readily accessible to HBV researchers, with international collaboration toward advancement and development of in vitro model systems for testing new HBV antivirals to ensure their pan-genotypic and/or customized activity.Keywords
Funding Information
- Poliomyelitis Research Foundation (16/29)
- Cancer Association of South Africa (2019)
- Deutsche Forschungsgemeinschaft (DFGR000)
This publication has 143 references indexed in Scilit:
- A New Class of Synthetic Peptide Inhibitors Blocks Attachment and Entry of Human Pathogenic VirusesThe Journal of Infectious Diseases, 2012
- The hepatitis B virus HBx protein modulates cell cycle regulatory proteins in cultured primary human hepatocytesVirus Research, 2010
- Highly efficient generation of human hepatocyte-like cells from induced pluripotent stem cellsHepatology, 2009
- Characterization of increased drug metabolism activity in dimethyl sulfoxide (DMSO)-treated Huh7 hepatoma cellsXenobiotica, 2009
- The influence of hepatitis B virus genotype and subgenotype on the natural history of chronic hepatitis BHepatology International, 2008
- Hepatitis B virus infection initiates with a large surface protein-dependent binding to heparan sulfate proteoglycansHepatology, 2007
- Relationship of serological subtype, basic core promoter and precore mutations to genotypes/subgenotypes of hepatitis B virusJournal of Medical Virology, 2007
- Induction of Pluripotent Stem Cells from Mouse Embryonic and Adult Fibroblast Cultures by Defined FactorsCell, 2006
- Infection of a human hepatoma cell line by hepatitis B virusProceedings of the National Academy of Sciences of the United States of America, 2002
- Reproducible High Level Infection of Cultured Adult Human Hepatocytes by Hepatitis B Virus: Effect of Polyethylene Glycol on Adsorption and PenetrationVirology, 1993