TY - JOUR T1 - Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma JF - Life Science Alliance JO - Life Sci. Alliance DO - 10.26508/lsa.202101036 VL - 4 IS - 9 SP - e202101036 AU - Frank Jühling AU - Antonio Saviano AU - Clara Ponsolles AU - Laura Heydmann AU - Emilie Crouchet AU - Sarah C Durand AU - Houssein El Saghire AU - Emanuele Felli AU - Véronique Lindner AU - Patrick Pessaux AU - Nathalie Pochet AU - Catherine Schuster AU - Eloi R Verrier AU - Thomas F Baumert Y1 - 2021/09/01 UR - https://www.life-science-alliance.org/content/4/9/e202101036.abstract N2 - Chronic hepatitis B virus (HBV) infection is a major cause of hepatocellular carcinoma (HCC) world-wide. The molecular mechanisms of viral hepatocarcinogenesis are still partially understood. Here, we applied two complementary single-cell RNA-sequencing protocols to investigate HBV–HCC host cell interactions at the single cell level of patient-derived HCC. Computational analyses revealed a marked HCC heterogeneity with a robust and significant correlation between HBV reads and cancer cell differentiation. Viral reads significantly correlated with the expression of HBV-dependency factors such as HLF in different tumor compartments. Analyses of virus-induced host responses identified previously undiscovered pathways mediating viral carcinogenesis, such as E2F- and MYC targets as well as adipogenesis. Mapping of fused HBV–host cell transcripts allowed the characterization of integration sites in individual cancer cells. Collectively, single-cell RNA-Seq unravels heterogeneity and compartmentalization of both, virus and cancer identifying new candidate pathways for viral hepatocarcinogenesis. The perturbation of pro-carcinogenic gene expression even at low HBV levels highlights the need of HBV cure to eliminate HCC risk. ER -