RT Journal Article
SR Electronic
T1 Hepatitis B virus compartmentalization and single-cell differentiation in hepatocellular carcinoma
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e202101036
DO 10.26508/lsa.202101036
VO 4
IS 9
A1 Jühling, Frank
A1 Saviano, Antonio
A1 Ponsolles, Clara
A1 Heydmann, Laura
A1 Crouchet, Emilie
A1 Durand, Sarah C
A1 El Saghire, Houssein
A1 Felli, Emanuele
A1 Lindner, Véronique
A1 Pessaux, Patrick
A1 Pochet, Nathalie
A1 Schuster, Catherine
A1 Verrier, Eloi R
A1 Baumert, Thomas F
YR 2021
UL http://www.life-science-alliance.org/content/4/9/e202101036.abstract
AB 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.