Evidence for long-term association of virion-delivered HBV core protein with cccDNA independently of viral protein production.
CAM
ChIP
ChIP, chromatin immunoprecipitation
FA, formaldehyde
H3K27Ac, histone 3 lysine 27 acetylation
HBVΔX, HBx-deficient HBV
HBc
HBc, HBV core protein
Hepatitis B Virus
HuHep, liver-humanized mice
PHHs, primary human hepatocytes
cccDNA
cccDNA, covalently closed circular DNA
dHepaRG, differentiated HepaRG cells
rcDNA, relaxed circular DNA
Journal
JHEP reports : innovation in hepatology
ISSN: 2589-5559
Titre abrégé: JHEP Rep
Pays: Netherlands
ID NLM: 101761237
Informations de publication
Date de publication:
Oct 2021
Oct 2021
Historique:
received:
19
01
2021
revised:
02
06
2021
accepted:
21
06
2021
entrez:
19
8
2021
pubmed:
20
8
2021
medline:
20
8
2021
Statut:
epublish
Résumé
HBV persists in the nucleus of infected hepatocytes as a covalently closed circular DNA (cccDNA) episome that constitutes the template for viral RNA and protein synthesis. Both HBx and HBc (core) viral proteins associate with cccDNA but, while HBx is required for viral transcription, the role of HBc is still unclear. The aim of this study was to determine if HBc derived from incoming nucleocapsid can associate with cccDNA before the onset of viral transcription and protein production. Chromatin immunoprecipitation assays were performed in native conditions. In addition, differentiated HepaRG (dHepaRG) cells infected with HBx-deficient HBV were used to investigate if HBc delivered by incoming virions can associate with cccDNA. Our results indicate that HBc can associate with cccDNA in the absence of viral transcription and These results suggest that virion-delivered HBc may participate at an early stage of cccDNA formation and/or transcription. The hepatitis B virus genome is released into the nucleoplasm of infected cells after disassembly of the viral nucleocapsids at the nuclear membrane. Herein, we show for the first time that virion-delivered hepatitis B core protein, a component of the viral capsid, can stably associate with integrated viral DNA.
Sections du résumé
BACKGROUND & AIMS
OBJECTIVE
HBV persists in the nucleus of infected hepatocytes as a covalently closed circular DNA (cccDNA) episome that constitutes the template for viral RNA and protein synthesis. Both HBx and HBc (core) viral proteins associate with cccDNA but, while HBx is required for viral transcription, the role of HBc is still unclear. The aim of this study was to determine if HBc derived from incoming nucleocapsid can associate with cccDNA before the onset of viral transcription and protein production.
METHODS
METHODS
Chromatin immunoprecipitation assays were performed in native conditions. In addition, differentiated HepaRG (dHepaRG) cells infected with HBx-deficient HBV were used to investigate if HBc delivered by incoming virions can associate with cccDNA.
RESULTS
RESULTS
Our results indicate that HBc can associate with cccDNA in the absence of viral transcription and
CONCLUSION
CONCLUSIONS
These results suggest that virion-delivered HBc may participate at an early stage of cccDNA formation and/or transcription.
LAY SUMMARY
BACKGROUND
The hepatitis B virus genome is released into the nucleoplasm of infected cells after disassembly of the viral nucleocapsids at the nuclear membrane. Herein, we show for the first time that virion-delivered hepatitis B core protein, a component of the viral capsid, can stably associate with integrated viral DNA.
Identifiants
pubmed: 34409278
doi: 10.1016/j.jhepr.2021.100330
pii: S2589-5559(21)00106-3
pmc: PMC8363821
doi:
Types de publication
Journal Article
Langues
eng
Pagination
100330Informations de copyright
© 2021 The Authors.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.
Références
J Hepatol. 2016 Apr;64(1 Suppl):S41-S48
pubmed: 27084036
Nature. 2016 Mar 17;531(7594):386-9
pubmed: 26983541
Gastroenterology. 2019 Jan;156(2):311-324
pubmed: 30243618
Nat Rev Drug Discov. 2019 Nov;18(11):827-844
pubmed: 31455905
J Hepatol. 2011 Nov;55(5):996-1003
pubmed: 21376091
Hepatology. 2019 Apr;69(4):1398-1411
pubmed: 30365161
J Mol Biol. 2001 Mar 16;307(1):183-96
pubmed: 11243813
Gut. 2015 Dec;64(12):1972-84
pubmed: 26048673
JHEP Rep. 2020 Oct 14;3(1):100195
pubmed: 33385130
Sci Rep. 2018 Mar 29;8(1):5390
pubmed: 29599452
Gastroenterology. 2006 Mar;130(3):823-37
pubmed: 16530522
PLoS Pathog. 2016 Oct 26;12(10):e1005893
pubmed: 27783675
Antiviral Res. 2017 Sep;145:14-19
pubmed: 28709657