RT Journal Article
SR Electronic
T1 A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201900355
DO 10.26508/lsa.201900355
VO 2
IS 2
A1 Peter AC Wing
A1 Tamara Davenne
A1 Jochen Wettengel
A1 Alvina G Lai
A1 Xiaodong Zhuang
A1 Anindita Chakraborty
A1 Valentina D’Arienzo
A1 Catharina Kramer
A1 Chunkyu Ko
A1 James M Harris
A1 Sabrina Schreiner
A1 Martin Higgs
A1 Stephanie Roessler
A1 Joanna L Parish
A1 Ulrike Protzer
A1 Peter Balfe
A1 Jan Rehwinkel
A1 Jane A McKeating
YR 2019
UL https://www.life-science-alliance.org/content/2/2/e201900355.abstract
AB 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.