Authors
Daniela Stadler, Martin Kächele, Alisha N Jones, Julia Hess, Christian Urban, Jessica Schneider, Yuchen Xia, Andreas Oswald, Firat Nebioglu, Romina Bester, Felix Lasitschka, Marc Ringelhan, Chunkyu Ko, Wen‐Min Chou, Arie Geerlof, Maarten A van de Klundert, Jochen M Wettengel, Peter Schirmacher, Mathias Heikenwälder, Sabrina Schreiner, Ralf Bartenschlager, Andreas Pichlmair, Michael Sattler, Kristian Unger, Ulrike Protzer
Publication date
2021/6/4
Journal
EMBO reports
Volume
22
Issue
6
Pages
e49568
Description
Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Interferons can diminish HBV cccDNA via APOBEC3‐mediated deamination. Here, we show that overexpression of APOBEC3A alone is not sufficient to reduce HBV cccDNA that requires additional treatment of cells with interferon indicating involvement of an interferon‐stimulated gene (ISG) in cccDNA degradation. Transcriptome analyses identify ISG20 as the only type I and II interferon‐induced, nuclear protein with annotated nuclease activity. ISG20 localizes to nucleoli of interferon‐stimulated hepatocytes and is enriched on deoxyuridine‐containing single‐stranded DNA that mimics transcriptionally active, APOBEC3A‐deaminated HBV DNA. ISG20 expression is detected in human livers in acute, self‐limiting but not in chronic hepatitis B. ISG20 …
Total citations
Scholar articles
D Stadler, M Kächele, AN Jones, J Hess, C Urban… - EMBO reports, 2021