A dual role for SAMHD1 in regulating HBV cccDNA and RT-dependent particle genesis.
DNA, Circular
/ genetics
DNA, Viral
/ genetics
Gene Knockout Techniques
Hep G2 Cells
Hepatitis B virus
/ genetics
Hepatitis B, Chronic
/ enzymology
Humans
RNA-Directed DNA Polymerase
/ genetics
Reverse Transcription
/ genetics
SAM Domain and HD Domain-Containing Protein 1
/ genetics
Transcriptional Activation
Transfection
Virus Replication
/ genetics
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
04 2019
04 2019
Historique:
received:
21
02
2019
revised:
15
03
2019
accepted:
18
03
2019
entrez:
29
3
2019
pubmed:
29
3
2019
medline:
29
3
2019
Statut:
epublish
Résumé
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
Identifiants
pubmed: 30918010
pii: 2/2/e201900355
doi: 10.26508/lsa.201900355
pmc: PMC6438393
pii:
doi:
Substances chimiques
DNA, Circular
0
DNA, Viral
0
RNA-Directed DNA Polymerase
EC 2.7.7.49
SAM Domain and HD Domain-Containing Protein 1
EC 3.1.5.-
SAMHD1 protein, human
EC 3.1.5.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Medical Research Council
ID : MC_UU_00008/8
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/N023498/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G1100247
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0902418
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/R022011/1
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0801976
Pays : United Kingdom
Organisme : Medical Research Council
ID : MR/P009085/1
Pays : United Kingdom
Organisme : Medical Research Council
ID : G0400802
Pays : United Kingdom
Informations de copyright
© 2019 Wing et al.
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