An Immortalized Hepatocyte-like Cell Line (imHC) Accommodated Complete Viral Lifecycle, Viral Persistence Form, cccDNA and Eventual Spreading of a Clinically-Isolated HBV.
HBV
NTCP
cccDNA
cell culture
hepatitis B
hepatocyte
viral spreading
Journal
Viruses
ISSN: 1999-4915
Titre abrégé: Viruses
Pays: Switzerland
ID NLM: 101509722
Informations de publication
Date de publication:
16 10 2019
16 10 2019
Historique:
received:
10
09
2019
revised:
14
10
2019
accepted:
15
10
2019
entrez:
19
10
2019
pubmed:
19
10
2019
medline:
29
9
2020
Statut:
epublish
Résumé
More than 350 million people worldwide have been persistently infected with the hepatitis B virus (HBV). Chronic HBV infection could advance toward liver cirrhosis and hepatocellular carcinoma. The intervention with prophylactic vaccine and conventional treatment could suppress HBV, but could not completely eradicate it. The major obstacle for investigating curative antiviral drugs are the incompetence of hepatocyte models that should have closely imitated natural human infection. Here, we demonstrated that an immortalized hepatocyte-like cell line (imHC) could accommodate for over 30 days the entire life cycle of HBV prepared from either established cultured cells or clinically-derived fresh isolates. Normally, imHCs had intact interferon signaling with anti-viral action. Infected imHCs responded to treatments with direct-acting antiviral drugs (DAAs) and interferons (IFNs) by diminishing HBV DNA, the covalently closed circular DNA (cccDNA) surface antigen of HBV (HBsAg, aka the Australia antigen) and the hepatitis B viral protein (HBeAg). Notably, we could observe and quantify HBV spreading from infected cells to naïve cells using an imHC co-culture model. In summary, this study constructed a convenient HBV culture model that allows the screening for novel anti-HBV agents with versatile targets, either HBV entry, replication or cccDNA formation. Combinations of agents aiming at different targets should achieve a complete HBV eradication.
Identifiants
pubmed: 31623162
pii: v11100952
doi: 10.3390/v11100952
pmc: PMC6832882
pii:
doi:
Substances chimiques
DNA, Circular
0
DNA, Viral
0
Hepatitis B Surface Antigens
0
Hepatitis B e Antigens
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Déclaration de conflit d'intérêts
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Références
Arch Toxicol. 2017 Jan;91(1):439-452
pubmed: 27039104
J Gen Virol. 2009 Jan;90(Pt 1):127-35
pubmed: 19088281
Curr Protoc Stem Cell Biol. 2017 Aug 14;42:4A.13.1-4A.13.34
pubmed: 28806853
Antiviral Res. 2015 Oct;122:91-100
pubmed: 26272257
Sci Rep. 2016 Jul 08;6:29358
pubmed: 27386799
Hepatology. 1996 Mar;23(3):405-13
pubmed: 8617418
J Virol Methods. 2014 Jan;195:185-93
pubmed: 24134944
Gastroenterology. 2012 Jun;142(7):1447-50.e3
pubmed: 22426294
Proc Natl Acad Sci U S A. 1987 Feb;84(4):1005-9
pubmed: 3029758
Sci Rep. 2018 Mar 29;8(1):5351
pubmed: 29599491
Hepatol Int. 2016 Jan;10(1):1-98
pubmed: 26563120
Curr Opin Immunol. 2015 Oct;36:61-6
pubmed: 26186123
Methods Mol Biol. 2012;826:73-87
pubmed: 22167641
Hepatology. 2015 Dec;62(6):1893-908
pubmed: 26239691
Biomaterials. 2013 Feb;34(7):1781-9
pubmed: 23228427
J Hepatol. 2016 Apr;64(1 Suppl):S41-S48
pubmed: 27084036
Cell Mol Gastroenterol Hepatol. 2017 Nov 24;5(3):187-207
pubmed: 29379855
Cold Spring Harb Perspect Med. 2015 Jul 01;5(8):a021428
pubmed: 26134480
J Virol. 2018 Jul 17;92(15):
pubmed: 29793953
Mol Cell Biochem. 2006 Feb;283(1-2):181-9
pubmed: 16444601
Drug Metab Dispos. 2008 Jan;36(1):137-45
pubmed: 17954527
Expert Opin Drug Metab Toxicol. 2016;12(2):169-74
pubmed: 26612411
Antimicrob Agents Chemother. 2017 Sep 22;61(10):
pubmed: 28717041
Malar J. 2018 Jan 25;17(1):50
pubmed: 29370800
Nat Commun. 2017 Jul 25;8(1):125
pubmed: 28743900
Science. 2014 Mar 14;343(6176):1221-8
pubmed: 24557838
J Hepatol. 2016 Apr;64(1 Suppl):S117-S131
pubmed: 27084032
Cell. 1986 Oct 10;47(1):37-47
pubmed: 3019565
Pharmacol Ther. 2013 Apr;138(1):103-41
pubmed: 23333322
EBioMedicine. 2018 Sep;35:114-123
pubmed: 30120080
Hepatology. 2009 Jun;49(6):2031-43
pubmed: 19274752
Cell Biol Toxicol. 2012 Apr;28(2):69-87
pubmed: 22258563
Arch Toxicol. 2013 Aug;87(8):1315-530
pubmed: 23974980
Proc Natl Acad Sci U S A. 2002 Nov 26;99(24):15655-60
pubmed: 12432097
Nat Biotechnol. 2008 Jan;26(1):120-6
pubmed: 18026090
Elife. 2012 Nov 13;1:e00049
pubmed: 23150796
Viruses. 2017 Jun 21;9(6):
pubmed: 28635668
Microbiol Mol Biol Rev. 2000 Mar;64(1):51-68
pubmed: 10704474
J Hepatol. 2016 Apr;64(1 Suppl):S60-S70
pubmed: 27084038
Hepatology. 2010 Jun;51(6):1954-60
pubmed: 20301206
Cell Mol Gastroenterol Hepatol. 2017 Nov 22;5(2):131-144
pubmed: 29322086
Clin Liver Dis. 2016 Nov;20(4):737-749
pubmed: 27742011
Arch Toxicol. 2013 Apr;87(4):577-610
pubmed: 23242478
Antimicrob Agents Chemother. 1997 Aug;41(8):1715-20
pubmed: 9257747
J Hepatol. 2017 Apr;66(4):685-692
pubmed: 27890789
Sci Rep. 2017 Apr 04;7:45698
pubmed: 28374759
J Hepatol. 2014 Oct;61(4):867-75
pubmed: 24845614
J Hepatol. 2017 Mar;66(3):494-503
pubmed: 27746336
J Gastroenterol Hepatol. 2016 Feb;31(2):302-9
pubmed: 26414381
Gastroenterology. 2014 Apr;146(4):1070-83
pubmed: 24361467
J Virol. 2012 Sep;86(17):9443-53
pubmed: 22740403
World J Gastroenterol. 2013 Nov 21;19(43):7500-14
pubmed: 24282342
Gastroenterology. 1994 Mar;106(3):664-73
pubmed: 8119538
Gut. 2015 Dec;64(12):1972-84
pubmed: 26048673
Tissue Eng Part C Methods. 2015 Apr;21(4):413-22
pubmed: 25233394
Sci Rep. 2017 Nov 30;7(1):16616
pubmed: 29192196
FEBS Lett. 2016 Feb;590(3):419-27
pubmed: 26867650
J Virol. 2007 Oct;81(20):10897-904
pubmed: 17670822
Gastroenterology. 2019 Jan;156(2):338-354
pubmed: 30243619
Methods Mol Biol. 2017;1540:1-14
pubmed: 27975303
Curr Opin Virol. 2018 Jun;30:80-89
pubmed: 29777955
Hepatology. 2006 Mar;43(3):539-47
pubmed: 16496321
Curr Opin Virol. 2018 Jun;30:68-79
pubmed: 29775812
PLoS Negl Trop Dis. 2020 Nov 20;14(11):e0008835
pubmed: 33216752
Viruses. 2016 Sep 20;8(9):
pubmed: 27657111
Proc Natl Acad Sci U S A. 2014 Aug 19;111(33):12193-8
pubmed: 25092305
BMC Biotechnol. 2011 Sep 30;11:89
pubmed: 21961524
Hepatology. 2014 May;59(5):1726-37
pubmed: 24375637
J Hepatol. 2013 May;58(5):861-7
pubmed: 23246506
J Hepatol. 2016 Apr;64(1 Suppl):S17-S31
pubmed: 27084033
J Hepatol. 2003 Jun;38(6):736-44
pubmed: 12763365
Hepatology. 2012 Feb;55(2):373-83
pubmed: 21953491
Proc Natl Acad Sci U S A. 2010 Feb 16;107(7):3141-5
pubmed: 20133632
J Hepatol. 2017 Aug;67(2):370-398
pubmed: 28427875
Cell Host Microbe. 2013 Jul 17;14(1):104-15
pubmed: 23870318
Nat Commun. 2018 Feb 14;9(1):682
pubmed: 29445209
Gastroenterology. 2016 Jan;150(1):194-205
pubmed: 26416327
J Hepatol. 2016 Apr;64(1 Suppl):S32-S40
pubmed: 27084034