Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach.
Chronic hepatitis B virus
Epigenetic gene silencing
Functional cure
Hepatitis B surface antigen
Hepatocellular carcinoma
Journal
World journal of gastroenterology
ISSN: 2219-2840
Titre abrégé: World J Gastroenterol
Pays: United States
ID NLM: 100883448
Informations de publication
Date de publication:
21 Jun 2021
21 Jun 2021
Historique:
received:
29
01
2021
revised:
23
03
2021
accepted:
07
05
2021
entrez:
24
6
2021
pubmed:
25
6
2021
medline:
29
6
2021
Statut:
ppublish
Résumé
Global prophylactic vaccination programmes have helped to curb new hepatitis B virus (HBV) infections. However, it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular carcinoma. As such, HBV remains a serious health priority and the development of novel curative therapeutics is urgently needed. Chronic HBV infection has been attributed to the persistence of the covalently closed circular DNA (cccDNA) which establishes itself as a minichromosome in the nucleus of hepatocytes. As the viral transcription intermediate, the cccDNA is responsible for producing new virions and perpetuating infection. HBV is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic modifications. Two HBV proteins, X (HBx) and core (HBc) promote viral replication by modulating the cccDNA epigenome and regulating host cell responses. This includes viral and host gene expression, chromatin remodeling, DNA methylation, the antiviral immune response, apoptosis, and ubiquitination. Elimination of the cccDNA minichromosome would result in a sterilizing cure; however, this may be difficult to achieve. Epigenetic therapies could permanently silence the cccDNA minichromosome and promote a functional cure. This review explores the cccDNA epigenome, how host and viral factors influence transcription, and the recent epigenetic therapies and epigenome engineering approaches that have been described.
Identifiants
pubmed: 34163105
doi: 10.3748/wjg.v27.i23.3182
pmc: PMC8218364
doi:
Substances chimiques
DNA, Circular
0
DNA, Viral
0
Types de publication
Journal Article
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
3182-3207Informations de copyright
©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict-of-interest statement: The authors declare no conflict-of-interest.
Références
Curr Opin Virol. 2011 Dec;1(6):519-25
pubmed: 22328912
Mol Ther Nucleic Acids. 2020 Jun 5;20:480-490
pubmed: 32278307
Front Microbiol. 2016 Jan 06;6:1491
pubmed: 26779147
Virology. 1996 Nov 15;225(2):387-94
pubmed: 8918925
J Biol Chem. 2020 Feb 28;295(9):2888
pubmed: 32111723
Gut Pathog. 2020 Apr 24;12:23
pubmed: 32346400
Cell. 2007 Feb 23;128(4):693-705
pubmed: 17320507
Mol Ther. 2020 Jun 3;28(6):1432-1441
pubmed: 32348718
PLoS Pathog. 2013 Sep;9(9):e1003613
pubmed: 24068929
MMWR Morb Mortal Wkly Rep. 2018 Jul 20;67(28):773-777
pubmed: 30025413
Nat Rev Genet. 2009 Nov;10(11):805-11
pubmed: 19789556
Cancer Sci. 2006 Oct;97(10):977-83
pubmed: 16984372
Virus Genes. 1994 Jul;8(3):215-29
pubmed: 7975268
Intervirology. 2011;54(6):316-25
pubmed: 21242658
Antiviral Res. 2020 Aug;180:104824
pubmed: 32450266
Hepatology. 2004 Sep;40(3):727-37
pubmed: 15349913
J Virol. 2004 Jul;78(13):6908-14
pubmed: 15194767
J Cell Mol Med. 2021 Jan;25(2):840-854
pubmed: 33263949
Trends Biochem Sci. 2014 Jul;39(7):310-8
pubmed: 24947342
J Gen Virol. 2008 Aug;89(Pt 8):1819-1828
pubmed: 18632952
Nature. 2004 May 27;429(6990):457-63
pubmed: 15164071
Cancer Lett. 2019 Jul 10;454:158-170
pubmed: 30981758
Nature. 2016 Mar 17;531(7594):386-9
pubmed: 26983541
ACS Infect Dis. 2019 Oct 11;5(10):1657-1667
pubmed: 31525994
Blood. 2012 Jan 26;119(4):1008-17
pubmed: 22160379
RNA Biol. 2017 Oct 3;14(10):1389-1398
pubmed: 28267418
J Virol. 2014 Mar;88(5):2442-51
pubmed: 24335313
J Mol Cell Biol. 2020 May 18;12(4):263-276
pubmed: 31865380
Cold Spring Harb Perspect Biol. 2014 Apr 01;6(4):a018713
pubmed: 24691964
Virology. 1995 Dec 20;214(2):371-8
pubmed: 8553537
Nat Commun. 2018 Aug 29;9(1):3497
pubmed: 30158648
Mol Ther Nucleic Acids. 2018 Sep 7;12:242-253
pubmed: 30195763
Mol Immunol. 2020 Jul;123:32-39
pubmed: 32413787
Hepatology. 2013 Aug;58(2):762-76
pubmed: 23483589
Science. 2014 Mar 14;343(6176):1221-8
pubmed: 24557838
Nat Rev Genet. 2016 Jan;17(1):47-62
pubmed: 26666209
Viruses. 2017 May 22;9(5):
pubmed: 28531167
Mol Cell Biol. 1991 Mar;11(3):1353-9
pubmed: 1996097
Front Genet. 2013 Oct 14;4:202
pubmed: 24133502
J Gastroenterol. 2001 Oct;36(10):651-60
pubmed: 11686474
EMBO J. 1986 Aug;5(8):1967-71
pubmed: 3463507
J Gen Virol. 2015 Aug;96(8):2252-2261
pubmed: 25904148
Hepatology. 2020 Sep;72(3):1142-1144
pubmed: 32502295
J Infect Dis. 2010 Sep 1;202(5):700-4
pubmed: 20653444
Genes (Basel). 2020 Sep 23;11(10):
pubmed: 32977396
J Virol. 2001 Sep;75(18):8400-6
pubmed: 11507185
J Virol. 2012 Sep;86(18):10059-69
pubmed: 22787202
Gastroenterology. 2013 Dec;145(6):1209-14
pubmed: 24042096
J Biol Chem. 2007 Feb 16;282(7):4277-4287
pubmed: 17158882
Nucleic Acids Res. 2014 Jun;42(10):6578-90
pubmed: 24705650
PLoS One. 2017 Jan 17;12(1):e0169648
pubmed: 28095508
J Cancer. 2019 Oct 20;10(25):6457-6465
pubmed: 31772678
J Virol. 2005 Apr;79(7):4238-45
pubmed: 15767425
Cell Death Differ. 2009 Feb;16(2):219-29
pubmed: 18927587
Antimicrob Agents Chemother. 2012 Aug;56(8):4277-88
pubmed: 22644022
J Biol Chem. 1997 Jul 4;272(27):16934-9
pubmed: 9202004
Proc Natl Acad Sci U S A. 2015 Oct 20;112(42):E5715-24
pubmed: 26438841
World J Gastroenterol. 2019 Jul 7;25(25):3136-3150
pubmed: 31333307
Emerg Microbes Infect. 2020 Dec;9(1):2455-2464
pubmed: 33084547
Hepatology. 2017 Dec;66(6):2066-2077
pubmed: 28833361
Int J Mol Sci. 2019 Sep 01;20(17):
pubmed: 31480501
PLoS Pathog. 2018 Jun 21;14(6):e1007124
pubmed: 29928064
Oncogene. 2006 Aug 28;25(38):5220-7
pubmed: 16936740
Hepatol Res. 2008 Jan;38(1):79-84
pubmed: 17645519
Hepatology. 2000 Jul;32(1):139-46
pubmed: 10869302
Antiviral Res. 2018 Jan;149:211-220
pubmed: 29183719
EMBO Rep. 2018 Oct;19(10):
pubmed: 30104204
Cell. 2013 Jan 17;152(1-2):132-43
pubmed: 23332751
Proc Natl Acad Sci U S A. 1990 Jul;87(13):5069-73
pubmed: 2367525
Hepatology. 2011 May;53(5):1476-85
pubmed: 21520166
Lancet Gastroenterol Hepatol. 2018 Jun;3(6):383-403
pubmed: 29599078
Nat Cell Biol. 2007 Jan;9(1):25-35
pubmed: 17159999
J Virol Methods. 1988 Mar-Apr;19(3-4):257-63
pubmed: 2836461
Mol Med Rep. 2019 Sep;20(3):2285-2293
pubmed: 31257511
Proc Natl Acad Sci U S A. 1993 Jul 15;90(14):6459-63
pubmed: 8341655
J Virol. 2019 Mar 5;93(6):
pubmed: 30567989
Biochim Biophys Acta Gene Regul Mech. 2017 Apr;1860(4):491-501
pubmed: 28242208
J Hepatol. 2009 Feb;50(2):377-87
pubmed: 19070387
PLoS Pathog. 2010 Sep 02;6(9):e1001082
pubmed: 20824087
Cell Mol Life Sci. 2019 May;76(9):1779-1794
pubmed: 30673820
Cell Rep. 2016 Sep 13;16(11):2846-2854
pubmed: 27626656
Nat Rev Mol Cell Biol. 2009 Mar;10(3):192-206
pubmed: 19234478
PLoS One. 2014 Oct 22;9(10):e110442
pubmed: 25337821
Biochem Cell Biol. 2002;80(4):445-55
pubmed: 12234098
Biochemistry (Mosc). 2014 Feb;79(2):111-23
pubmed: 24794726
J Virol. 2017 Apr 28;91(10):
pubmed: 28148795
Trends Biochem Sci. 1998 May;23(5):174-8
pubmed: 9612081
Proc Natl Acad Sci U S A. 2016 Sep 13;113(37):10388-93
pubmed: 27582466
Nat Rev Genet. 2016 Aug;17(8):487-500
pubmed: 27346641
J Viral Hepat. 2008 Feb;15(2):103-7
pubmed: 18184192
Elife. 2012 Nov 13;1:e00049
pubmed: 23150796
Mol Med Rep. 2016 Jan;13(1):301-8
pubmed: 26573490
Virol Sin. 2021 Feb;36(1):163-166
pubmed: 32632817
Mol Ther. 2013 Oct;21(10):1889-97
pubmed: 23883864
Biol Chem. 2003 Feb;384(2):203-12
pubmed: 12675512
Clin Epigenetics. 2020 Sep 7;12(1):135
pubmed: 32894195
Life Sci. 2020 Sep 15;257:118089
pubmed: 32659369
Hepatology. 2016 Dec;64(6):2246-2249
pubmed: 27639252
Hepatology. 2008 Aug;48(2):361-73
pubmed: 18615500
IUBMB Life. 2019 Sep;71(9):1336-1346
pubmed: 31018043
Int J Mol Sci. 2018 Feb 14;19(2):
pubmed: 29443889
Cell Microbiol. 2009 Apr;11(4):645-60
pubmed: 19141126
Theranostics. 2019 Jul 9;9(18):5227-5245
pubmed: 31410212
Nature. 2012 Jul 25;487(7408):439-40
pubmed: 22836995
J Virol. 2008 Apr;82(8):3814-21
pubmed: 18234786
J Med Virol. 2009 Jul;81(7):1177-83
pubmed: 19475606
Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4244-53
pubmed: 25201958
Virology. 2014 Aug;462-463:149-57
pubmed: 24992041
J Virol. 1989 Sep;63(9):4019-26
pubmed: 2788226
Antiviral Res. 2019 Aug;168:146-155
pubmed: 31018112
Adv Drug Deliv Rev. 2021 Jan;168:134-146
pubmed: 32485207
PLoS Genet. 2009 Mar;5(3):e1000435
pubmed: 19325889
J Mol Biol. 2001 Mar 16;307(1):183-96
pubmed: 11243813
Epigenetics. 2012 Sep;7(9):994-1007
pubmed: 22894906
Oncogene. 2003 Dec 8;22(56):9030-40
pubmed: 14663481
Cell Microbiol. 2017 May;19(5):
pubmed: 27886437
Virus Res. 2008 Jun;134(1-2):235-49
pubmed: 18339439
J Clin Invest. 2012 Feb;122(2):529-37
pubmed: 22251702
Biomed Pharmacother. 2018 Mar;99:576-582
pubmed: 29902868
J Virol. 2000 Jun;74(12):5562-8
pubmed: 10823863
Life Sci. 2019 Feb 15;219:199-208
pubmed: 30615846
J Virol. 2017 Aug 10;91(17):
pubmed: 28637752
Cell Div. 2012 Mar 14;7(1):10
pubmed: 22417103
PLoS One. 2012;7(3):e34165
pubmed: 22479552
Hepatology. 2019 Mar;69(3):974-992
pubmed: 30180281
BMC Genomics. 2012 Oct 22;13:563
pubmed: 23088787
J Exp Clin Cancer Res. 2020 Jun 1;39(1):97
pubmed: 32487115
Gastroenterology. 2007 Apr;132(4):1476-94
pubmed: 17408664
J Virol. 2015 Feb;89(4):2041-51
pubmed: 25428880
J Hepatol. 2016 Apr;64(1 Suppl):S84-S101
pubmed: 27084040
J Biol Chem. 2002 Mar 22;277(12):9982-8
pubmed: 11788598
Virology. 1994 Nov 1;204(2):600-8
pubmed: 7941327
PLoS One. 2013;8(2):e56711
pubmed: 23451072
FASEB J. 2011 Dec;25(12):4511-21
pubmed: 21903935
J Virol. 2019 May 15;93(11):
pubmed: 30867306
Genes (Basel). 2018 Apr 12;9(4):
pubmed: 29649127
Virus Evol. 2020 Aug 25;7(1):veaa063
pubmed: 33732502
Cancer Lett. 2003 Feb 20;190(2):213-9
pubmed: 12565176
Virol Sin. 2017 Dec;32(6):454-464
pubmed: 29280054
J Hepatol. 2009 Sep;51(3):581-92
pubmed: 19616338
J Hepatol. 2005 Mar;42(3):302-8
pubmed: 15710212
Mol Ther. 2016 Aug;24(7):1258-66
pubmed: 27203444
Virus Res. 2016 Jul 15;220:150-60
pubmed: 27132039
J Virol. 2017 Jul 27;91(16):
pubmed: 28592528
Hepatology. 2018 May;67(5):1695-1709
pubmed: 29194684
Trends Biochem Sci. 2009 Nov;34(11):562-70
pubmed: 19818632
Cell Microbiol. 2020 Mar;22(3):e13148
pubmed: 31829498
Hepatology. 2020 May;71(5):1678-1695
pubmed: 31544250
Life Sci Alliance. 2019 Mar 27;2(2):
pubmed: 30918010
J Mol Diagn. 2018 May;20(3):334-343
pubmed: 29656833
Gut. 2015 Dec;64(12):1972-84
pubmed: 26048673
Nucleic Acids Res. 2020 Dec 16;48(22):12453-12482
pubmed: 33196851
Exp Cell Res. 2018 Oct 1;371(1):92-103
pubmed: 30059664
Cell Biochem Funct. 2020 Jun;38(4):436-442
pubmed: 31930529
PLoS One. 2017 Mar 20;12(3):e0174017
pubmed: 28319127
J Biol Chem. 2004 Nov 12;279(46):48350-9
pubmed: 15339928
Nat Microbiol. 2020 May;5(5):715-726
pubmed: 32152586
Curr Biol. 2005 Jul 12;15(13):1235-41
pubmed: 16005298
Theranostics. 2019 Sep 25;9(24):7345-7358
pubmed: 31695772
Viruses. 2019 May 09;11(5):
pubmed: 31075894
PLoS Pathog. 2019 Apr 26;15(4):e1007742
pubmed: 31026293
Methods Mol Biol. 2018;1708:515-535
pubmed: 29224161
DNA Cell Biol. 1998 Nov;17(11):951-6
pubmed: 9839804
J Infect Dis. 2020 Apr 7;221(9):1462-1469
pubmed: 31740931
Hepatology. 2017 Aug;66(2):398-415
pubmed: 28236308
Int J Mol Med. 2018 Apr;41(4):2169-2176
pubmed: 29344646
Cell. 2013 Feb 14;152(4):859-72
pubmed: 23415232
J Biol Chem. 2017 Dec 15;292(50):20379-20393
pubmed: 29046350
J Hepatol. 2015 Nov;63(5):1093-102
pubmed: 26143443
Nat Rev Mater. 2019 Nov;4:726-737
pubmed: 34094589
Sci Rep. 2017 Jan 11;7:40246
pubmed: 28074857
Hepatology. 2018 Oct;68(4):1260-1276
pubmed: 29624717
FASEB J. 2014 Mar;28(3):1454-63
pubmed: 24297698
FASEB J. 2018 Oct;32(10):5737-5750
pubmed: 29763382
DNA Cell Biol. 2011 Jun;30(6):347-54
pubmed: 21345131
Gut. 2020 Nov;69(11):2016-2024
pubmed: 32114505
Cells. 2020 Mar 30;9(4):
pubmed: 32235678
Proc Natl Acad Sci U S A. 2009 Nov 24;106(47):19975-9
pubmed: 19906987
Oncol Rep. 2011 Nov;26(5):1281-6
pubmed: 21725618
J Virol. 1992 Dec;66(12):6912-21
pubmed: 1331502
Crit Rev Eukaryot Gene Expr. 1999;9(1):19-32
pubmed: 10200909
Nature. 2000 Jan 6;403(6765):41-5
pubmed: 10638745
J Biomol Screen. 2013 Apr;18(4):378-87
pubmed: 23042077
J Microbiol Biotechnol. 2016 Apr 28;26(4):637-47
pubmed: 26699741
J Virol. 2019 Mar 5;93(6):
pubmed: 30567987
Sci Rep. 2017 Aug 7;7(1):7401
pubmed: 28785016
J Virol. 2013 Apr;87(8):4360-71
pubmed: 23388725
Genes Dev. 2009 Apr 1;23(7):781-3
pubmed: 19339683
J Gen Virol. 2009 May;90(Pt 5):1246-1255
pubmed: 19264593
JHEP Rep. 2020 Oct 14;3(1):100195
pubmed: 33385130
J Virol. 1999 Sep;73(9):7231-40
pubmed: 10438810
J Hepatol. 2021 Mar;74(3):522-534
pubmed: 32987030
Cell Immunol. 2019 Feb;336:66-74
pubmed: 30626493
PLoS Pathog. 2016 Oct 26;12(10):e1005893
pubmed: 27783675
Nat Cell Biol. 2021 Jan;23(1):11-22
pubmed: 33420494
Gut Liver. 2013 Sep;7(5):569-75
pubmed: 24073315
Int J Med Sci. 2018 Sep 7;15(12):1356-1364
pubmed: 30275764
Antiviral Res. 2017 Aug;144:1-7
pubmed: 28499864
Virology. 1994 Nov 15;205(1):127-32
pubmed: 7975208
BMC Infect Dis. 2019 Sep 12;19(1):802
pubmed: 31510934
J Biol Chem. 2005 Apr 8;280(14):13341-8
pubmed: 15671018
Science. 2006 Jan 20;311(5759):395-8
pubmed: 16424344
J Virol. 1997 Dec;71(12):9392-9
pubmed: 9371599
Science. 1993 Apr 16;260(5106):309-10
pubmed: 8469984
Lancet Gastroenterol Hepatol. 2019 Jul;4(7):545-558
pubmed: 30981686
PLoS Pathog. 2017 Dec 29;13(12):e1006784
pubmed: 29287110
Sci Rep. 2015 May 22;5:10478
pubmed: 26000761
Proc Natl Acad Sci U S A. 2002 Dec 24;99(26):16916-21
pubmed: 12481029
Nat Struct Mol Biol. 2010 Jan;17(1):105-11
pubmed: 19966799
J Infect Dis. 2009 May 1;199(9):1286-91
pubmed: 19301974
Epigenetics. 2011 Jun;6(6):720-6
pubmed: 21546797
Virology. 1990 Mar;175(1):255-61
pubmed: 2155510
Biochem Biophys Res Commun. 2010 Aug 6;398(4):771-7
pubmed: 20633528
Cell. 2007 Nov 16;131(4):633-6
pubmed: 18022353
Hepatology. 2021 Feb;73(2):486-502
pubmed: 32333814
Cell Physiol Biochem. 2017;41(1):310-322
pubmed: 28135713
Virology. 1995 Apr 1;208(1):399-404
pubmed: 11831727
DNA Cell Biol. 2015 May;34(5):327-32
pubmed: 25664994
Oncotarget. 2016 Mar 29;7(13):16003-11
pubmed: 26895378
Am J Physiol Gastrointest Liver Physiol. 2011 May;300(5):G771-81
pubmed: 21330447
Br J Cancer. 2008 Jun 17;98(12):1881-5
pubmed: 18542062
Cell. 2013 May 23;153(5):1012-24
pubmed: 23706739
Hepatology. 2012 Mar;55(3):730-41
pubmed: 22105316
Virus Res. 1997 May;49(1):1-7
pubmed: 9178491
Cold Spring Harb Perspect Med. 2016 Mar 01;6(3):a026104
pubmed: 26931810
J Virol. 2018 Mar 14;92(7):
pubmed: 29321333
J Virol. 1995 Jun;69(6):3647-57
pubmed: 7745713
Nat Rev Genet. 2012 May 29;13(7):484-92
pubmed: 22641018
Front Microbiol. 2018 Jul 18;9:1611
pubmed: 30072974
Semin Immunopathol. 2020 Apr;42(2):173-185
pubmed: 32185454
J Virol. 2020 Aug 17;94(17):
pubmed: 32581092
Nat Med. 2019 Feb;25(2):249-254
pubmed: 30692695
J Hepatol. 2012 Jan;56(1):26-33
pubmed: 21703183
Antiviral Res. 2015 Sep;121:82-93
pubmed: 26129969
Sci Rep. 2016 May 03;6:25389
pubmed: 27138288
Sci Rep. 2020 Dec 3;10(1):21097
pubmed: 33273565
Sci Rep. 2015 Jun 02;5:10833
pubmed: 26035283
J Viral Hepat. 2010 Aug;17(8):527-36
pubmed: 20546497
J Virol. 2010 May;84(9):4321-9
pubmed: 20147412
J Virol. 1995 Jun;69(6):3350-7
pubmed: 7745682
J Viral Hepat. 2009 Aug;16(8):537-46
pubmed: 19302415
J Gen Virol. 2003 Aug;84(Pt 8):2073-2082
pubmed: 12867637
FEBS Lett. 2015 Oct 7;589(20 Pt A):2914-22
pubmed: 25980611
Gastroenterology. 2006 Mar;130(3):823-37
pubmed: 16530522
Proc Natl Acad Sci U S A. 1995 Apr 25;92(9):3819-23
pubmed: 7731990
Int J Mol Sci. 2013 Jul 31;14(8):16010-39
pubmed: 23912238
Sci Signal. 2012 Jan 03;5(205):ra1
pubmed: 22215732
Front Immunol. 2018 Sep 11;9:2080
pubmed: 30254645