A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis
| Autor: | Wing, P, Davenne, T, Wettengel, J, Lai, A, Zhuang, X, Chakraborty, A, D'Arienzo, V, Kramer, C, Ko, C, Harris, J, Schreiner, S, Higgs, M, Roessler, S, Parish, J, Protzer, U, Balfe, P, Rehwinkel, J, McKeating, J |
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| Rok vydání: | 2019 |
| Předmět: | |
| Zdroj: | Life Science Alliance |
| ISSN: | 2575-1077 |
| DOI: | 10.26508/lsa.201900355 |
| Popis: | Our study highlights a dual role for SAMHD1 in regulating hepatitis B virus cccDNA levels and reverse transcriptase–dependent particle genesis. 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. |
| Databáze: | OpenAIRE |
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