Liver-Derived Cell Transfection Model Efficacy for HBV Genotype B Replication/Transcription Is Determined by Complex Host Transcription Factor Network

Background: Interaction between host transcription factors (TFs) and the viral genome is fundamental for hepatitis B virus (HBV) gene expression regulation. Additionally, the distinct interaction of the TFs’ network with the HBV genome determines the regulatory effect outcome. Hence, different HBV genotypes and their variants may display different viral replication/transcription regulation. Due to the lack of an efficient infection model suitable for all HBV genotypes, the hepatoma cell transfection model is primarily used in studies involving non-D HBV genotypes and variants. Methods: We explored the transcriptome profile of host TFs with a regulatory effect on HBV in eight liver-derived cell lines in comparison with primary human hepatocytes (PHH). We further analyzed the suitability of these models in supporting HBV genotype B replication/transcription. Results: Among studied models, HC-04, as a result of the close similarity of TFs transcriptome profile to PHH and the interaction of specific TFs including HNF4α and PPARα, showed the highest efficiency in regard to viral replication and antigen production. The absence of TFs expression in L02 transfection model resulted in its inefficiency in HBV replication/transcription. Conclusion: These observations help to better design studies on regulatory mechanisms involving non-D HBV genotypes and variants’ gene expression and the development of more efficient therapeutical approaches.