Fig. 4

HBV life cycle and the unpublished data of suppression of HBV expression in the PDO model. A HBV life cycle. HBV enters hepatocytes by membrane fusion and internalization through NTCP, followed by uncoating, and nuclear transport of the RC DNA. The RC DNA is converted to cccDNA, which serves as a template for the transcription of pregenomic HBV RNA and generates 4 different mRNA transcripts: 3.5 kb preC RNA and pgRNA, 2.4 and 2.1 kb preS/S mRNAs, and 0.7 kb HBx mRNA. These RNAs are exported to the cytoplasm, and plenty of HBV proteins are generated. pgRNA is selectively packaged inside core particles, followed by several progresses to generate RC DNA. Following viral assembly in the endoplasmic reticulum, mature HBV is released into the extracellular matrix. B Time course of relative HBsAg levels in expansion medium in the PDO model generated from patients infected with HBV. Error bars represent the mean ± SEM. C Heatmap of NTCP mRNA levels relative to GAPDH of different supplements added into basic medium with HEPES, B27, N2, Glutamax, N-acetyl-l-cysteine, EGF, FGF10 and HGF