Transcriptomic analysis of lipid biosynthesis pathways for HBV cure

RNAseq analysis of liver tissue samples from uninfected (n=5) and HBV-infected (n=5) humanized chimeric liver (uPA/SCID) mice was performed to identify potential new host factors and pathways modulated by HBV infection Human liver-chimeric uPA/SCID mice were generated by PhoenixBio Co., Ltd. (Higashi-Hiroshima, Japan). Human hepatocytes were derived from donor BD195 (BD Biosciences, Woburn, MA). Mice containing human hepatocytes with a mean estimated replacement index of 86% (range 83-90%), calculated based on the blood concentration of human albumin [h-Alb]), were infected with 1x105 copies/mouse of HBV genotype C and followed for eight weeks to establish persistent infection of the human hepatocytes in the chimeric liver. At baseline (day 0 post-infection), mean body weights across all randomized mice were 18.0 g (19.0 - 21.1 g) with average serum levels of h-Alb of 10.0 mg/mL (9.2 - 11.9 mg/mL). Throughout the infection, all mice maintained a body weight of more than 90% of the initial level (HBV-inoculated group ranged from 90% (17.6 g) to 110% (21.6 g) to that in the control group) and an average blood h-Alb concentration of more than 10 mg/mL (HBV-inoculated group ranged from 90% (9.7 mg/mL) to 110% (11.9 mg/mL) to that in the control group).