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Wing, P.A.* ; Davenne, T.* ; Wettengel, J.M. ; Lai, A.G.* ; Zhuang, X.* ; Chakraborty, A. ; D'Arienzo, V.* ; Kramer, C.* ; Ko, C. ; Harris, J.M.* ; Schreiner, S. ; Higgs, M.* ; Roessler, S.* ; Parish, J.L.* ; Protzer, U. ; Balfe, P.* ; Rehwinkel, J.* ; McKeating, J.A.*

A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis.

Life Sci. All. 2:e201900355 (2019)
Verlagsversion DOI PMC
Open Access Gold
Creative Commons Lizenzvertrag
Chronic hepatitis B is one of the world’s unconquered diseases with more than 240 million infected subjects at risk of developing liver disease and hepatocellular carcinoma. Hepatitis B virus reverse transcribes pre-genomic RNA to relaxed circular DNA (rcDNA) that comprises the infectious particle. To establish infection of a naïve target cell, the newly imported rcDNA is repaired by host enzymes to generate covalently closed circular DNA (cccDNA), which forms the transcriptional template for viral replication. SAMHD1 is a component of the innate immune system that regulates deoxyribonucleoside triphosphate levels required for host and viral DNA synthesis. Here, we show a positive role for SAMHD1 in regulating cccDNA formation, where KO of SAMHD1 significantly reduces cccDNA levels that was reversed by expressing wild-type but not a mutated SAMHD1 lacking the nuclear localization signal. The limited pool of cccDNA in infected Samhd1 KO cells is transcriptionally active, and we observed a 10-fold increase in newly synthesized rcDNA-containing particles, demonstrating a dual role for SAMHD1 to both facilitate cccDNA genesis and to restrict reverse transcriptase-dependent particle genesis.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Korrespondenzautor
ISSN (print) / ISBN 2575-1077
e-ISSN 2575-1077
Zeitschrift Life Science Alliance
Quellenangaben Band: 2, Heft: 2, Seiten: , Artikelnummer: e201900355 Supplement: ,
Verlag EMBO Press
Verlagsort Heidelberg
Nichtpatentliteratur Publikationen
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Virology (VIRO)