Long-Term Hepatitis B Virus Infection Induces Cytopathic Effects in Primary Human Hepatocytes, and Can be Partially Reversed by Antiviral Therapy

Based on our recently developed 5 chemicals-cultured primary human hepatocytes (5C-PHH) model that supports long-term HBV infection, we performed multiplexed quantitative analysis of temporal changes of host proteome and transcriptome on PHH cells infected by HBV for up to 4 weeks. We showed that metabolic-, complement-, cytoskeleton-, mitochondrial- and oxidation-related pathways were modulated at transcriptional or post-transcriptional levels during long-term HBV infection, which led to cytopathic effects and could be partially rescued by early rather than late nucleot(s)ide analogs (NAs) administration. Mock- and HBV- infected (ayw, MOI 200) 5C-PHH to quantify kinetics of changes mRNA expression by RNA sequencing in triplicate at 2, 7, and 28 dpi; entecavir (ETV) to treat the cells (at 100 nM) right away following HBV infection, and samples were collected at 7 and 28 dpi for RNA-seq analysis.