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HBV cccDNA的体外细胞模型和实验小鼠模型

苏瑜 朱园飞 田青右 谢幼华 邓强

引用本文:
Citation:

HBV cccDNA的体外细胞模型和实验小鼠模型

DOI: 10.3969/j.issn.1001-5256.2019.06.007
基金项目: 

国家自然科学基金项目(81672034,81871647); 上海市教育委员会科研创新计划项目(2017-01-07-00-07-E00057); 传染病国家科技重大专项(2018ZX10301208); 

详细信息
  • 中图分类号: R512.62;R-332

In vitro cell model and mouse model of HBV cccDNA

Research funding: 

 

  • 摘要: HBV慢性感染仍然是世界性公共健康问题。现有抗病毒药物能够有效抑制HBV复制,却无法使之完全治愈。共价闭合环状DNA(cccDNA)是HBV复制的原始模版,具有显著的稳定性,是HBV持续感染的分子基础,也是实现感染治愈的关键靶点。由于较低的细胞内拷贝数,以及缺乏灵敏可靠的检测方法,限制了对HBV cccDNA生物合成、代谢和调控等方面的相关研究。建立合适的cccDNA研究模型有助于了解这些生物学过程。综述了近年来HBV cccDNA细胞培养模型和实验小鼠模型等方面的主要进展,以期为进一步研究HBV病毒学和抗病毒药物研发提供帮助。

     

  • [1]BECK J, NASSAL M.Hepatitis B virus replication[J].World JGastroenterol, 2007, 13 (1) :48-64.
    [2]YANG W, SUMMERS J.Illegitimate replication of linear hepadnavirus DNA through nonhomologous recombination[J].J Virol, 1995, 69 (7) :4029-4036.
    [3]GAO W, HU J.Formation of hepatitis B virus covalently closed circular DNA:Removal of genome-linked protein[J].J Virol, 2007, 81 (12) :6164-6174.
    [4]GUO H, JIANG D, ZHOU T, et al.Characterization of the intracellular deproteinized relaxed circular DNA of hepatitis B virus:An intermediate of covalently closed circular DNA formation[J].J Virol, 2007, 81 (22) :12472-12484.
    [5]BOCK CT, SCHWINN S, LOCARNINI S, et al.Structural organization of the hepatitis B virus minichromosome[J].J Mol Biol, 2001, 307 (1) :183-196.
    [6]HONG X, KIM ES, GUO H.Epigenetic regulation of hepatitis B virus covalently closed circular DNA:Implications for epigenetic therapy against chronic hepatitis B[J].Hepatology, 2017, 66 (6) :2066-2077.
    [7]WERLE-LAPOSTOLLE B, BOWDEN S, LOCARNINI S, et al.Persistence of cccDNA during the natural history of chronic hepatitis Band decline during adefovir dipivoxil therapy[J].Gastroenterology, 2004, 126 (7) :1750-1758.
    [8]BOURNE EJ, DIENSTAG JL, LOPEZ VA, et al.Quantitative analysis of HBV cccDNA from clinical specimens:Correlation with clinical and virological response during antiviral therapy[J].J Viral Hepat, 2007, 14 (1) :55-63.
    [9]ALLWEISS L, DANDRI M.The role of cccDNA in HBV maintenance[J].Viruses, 2017, 9 (6) :e156.
    [10]CHEN X, OIDOVSAMBUU O, LIU P, et al.A novel quantitative microarray antibody capture assay identifies an extremely high hepatitis delta virus prevalence among hepatitis B virusinfected mongolians[J].Hepatology, 2017, 66 (6) :1739-1749.
    [11]WIELAND S, THIMME R, PURCELL RH, et al.Genomic analysis of the host response to hepatitis B virus infection[J].Proc Natl Acad Sci U S A, 2004, 101 (17) :6669-6674.
    [12]LUCIFORA J, XIA Y, REISINGER F, et al.Specific and nonhepatotoxic degradation of nuclear hepatitis B virus cccDNA[J].Science, 2014, 343 (6176) :1221-1228.
    [13]SHEN F, LI Y, WANG Y, et al.Hepatitis B virus sensitivity to interferon-alpha in hepatocytes is more associated with cellular interferon response than with viral genotype[J].Hepatology, 2018, 67 (4) :1237-1252.
    [14]GRIPON P, DIOT C, THEZE N, et al.Hepatitis B virus infection of adult human hepatocytes cultured in the presence of dimethyl sulfoxide[J].J Virol, 1988, 62 (11) :4136-4143.
    [15]ORTEGA-PRIETO AM, SKELTON JK, WAI SN, et al.3D microfluidic liver cultures as a physiological preclinical tool for hepatitis B virus infection[J].Nat Commun, 2018, 9 (1) :682.
    [16]ZHANG K, ZHANG L, LIU W, et al.In vitro expansion of primary human hepatocytes with efficient liver repopulation capacity[J].Cell Stem Cell, 2018, 23 (6) :806-819, e804.
    [17]FU GB, HUANG WJ, ZENG M, et al.Expansion and differentiation of human hepatocyte-derived liver progenitor-like cells and their use for the study of hepatotropic pathogens[J].Cell Res, 2019, 29 (1) :8-22.
    [18]GRIPON P, RUMIN S, URBAN S, et al.Infection of a human hepatoma cell line by hepatitis B virus[J].Proc Natl Acad Sci U S A, 2002, 99 (24) :15655-15660.
    [19]HANTZ O, PARENT R, DURANTEL D, et al.Persistence of the hepatitis B virus covalently closed circular DNA in HepaRGhuman hepatocyte-like cells[J].J Gen Virol, 2009, 90 (Pt1) :127-135.
    [20]LUCIFORA J, DURANTEL D, TESTONI B, et al.Control of hepatitis B virus replication by innate response of HepaRG cells[J].Hepatology, 2010, 51 (1) :63-72.
    [21]ZHONG G, YAN H, WANG H, et al.Sodium taurocholate cotransporting polypeptide mediates woolly monkey hepatitis Bvirus infection of Tupaia hepatocytes[J].J Virol, 2013, 87 (12) :7176-7184.
    [22]YAN H, LI W.Sodium taurocholate cotransporting polypeptide acts as a receptor for hepatitis B and D virus[J].Dig Dis, 2015, 33 (3) :388-396.
    [23]NI Y, LEMPP FA, MEHRLE S, et al.Hepatitis B and D viruses exploit sodium taurocholate co-transporting polypeptide for species-specific entry into hepatocytes[J].Gastroenterology, 2014, 146 (4) :1070-1083.
    [24]QI Y, GAO Z, XU G, et al.DNA polymerase kappa is a key cellular factor for the formation of covalently closed circular DNA of hepatitis B virus[J].PLo S Pathog, 2016, 12 (10) :e1005893.
    [25]LONG Q, YAN R, HU J, et al.The role of host DNA ligases in hepadnavirus covalently closed circular DNA formation[J].PLo S Pathog, 2017, 13 (12) :e1006784.
    [26]GUIDOTTI LG, MATZKE B, SCHALLER H, et al.High-level hepatitis B virus replication in transgenic mice[J].J Virol, 1995, 69 (10) :6158-6169.
    [27]RANEY AK, EGGERS CM, KLINE EF, et al.Nuclear covalently closed circular viral genomic DNA in the liver of hepatocyte nuclear factor 1 alpha-null hepatitis B virus transgenic mice[J].J Virol, 2001, 75 (6) :2900-2911.
    [28]LI H, ZHUANG Q, WANG Y, et al.HBV life cycle is restricted in mouse hepatocytes expressing human NTCP[J].Cell Mol Immunol, 2014, 11 (2) :175-183.
    [29]BOGOMOLOV P, ALEXANDROV A, VORONKOVA N, et al.Treatment of chronic hepatitis D with the entry inhibitor myrcludex B:First results of a phase Ib/IIa study[J].J Hepatol, 2016, 65 (3) :490-498.
    [30]HE W, REN B, MAO F, et al.Hepatitis D virus infection of mice expressing human sodium taurocholate co-transporting polypeptide[J].PLo S Pathog, 2015, 11 (4) :e1004840.
    [31]CUI X, CLARK DN, LIU K, et al.Viral DNA-dependent induction of innate immune response to hepatitis B virus in immortalized mouse hepatocytes[J].J Virol, 2016, 90 (1) :486-496.
    [32]SUMMERS J, SMITH PM, HORWICH AL.Hepadnavirus envelope proteins regulate covalently closed circular DNA amplification[J].J Virol, 1990, 64 (6) :2819-2824.
    [33]SUMMERS J, SMITH PM, HUANG MJ, et al.Morphogenetic and regulatory effects of mutations in the envelope proteins of an avian hepadnavirus[J].J Virol, 1991, 65 (3) :1310-1317.
    [34]KOCK J, ROSLER C, ZHANG JJ, et al.Generation of covalently closed circular DNA of hepatitis B viruses via intracellular recycling is regulated in a virus specific manner[J].PLo SPathog, 2010, 6 (9) :e1001082.
    [35]SELLS MA, CHEN ML, ACS G.Production of hepatitis B virus particles in Hep G2 cells transfected with cloned hepatitis B virus DNA[J].Proc Natl Acad Sci U S A, 1987, 84 (4) :1005-1009.
    [36]LADNER SK, OTTO MJ, BARKER CS, et al.Inducible expression of human hepatitis B virus (HBV) in stably transfected hepatoblastoma cells:A novel system for screening potential inhibitors of HBV replication[J].Antimicrob Agents Chemother, 1997, 41 (8) :1715-1720.
    [37]GUO JT, GUO H.Metabolism and function of hepatitis B virus cccDNA:Implications for the development of cccDNA-targeting antiviral therapeutics[J].Antiviral Res, 2015, 122:91-100.
    [38]CAI D, WANG X, YAN R, et al.Establishment of an inducible HBV stable cell line that expresses cccDNA-dependent epitope-tagged HBe Ag for screening of cccDNA modulators[J].Antiviral Res, 2016, 132:26-37.
    [39]GNTHER S, LI BC, MISKA S, et al.A novel method for efficient amplification of whole hepatitis B virus genomes permits rapid functional analysis and reveals deletion mutants in immunosuppressed patients[J].J Virol, 1995, 69 (9) :5437-5444.
    [40]POLLICINO T, BELLONI L, RAFFA G, et al.Hepatitis B virus replication is regulated by the acetylation status of hepatitis Bvirus cccDNA-bound H3 and H4 histones[J].Gastroenterology, 2006, 130 (3) :823-837.
    [41]BELLONI L, POLLICINO T, de NICOLA F, et al.Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function[J].Proc Natl Acad Sci U S A, 2009, 106 (47) :19975-19979.
    [42]BELLONI L, ALLWEISS L, GUERRIERI F, et al.IFN-alpha inhibits HBV transcription and replication in cell culture and in humanized mice by targeting the epigenetic regulation of the nuclear cccDNA minichromosome[J].J Clin Invest, 2012, 122 (2) :529-537.
    [43]QI Z, LI G, HU H, et al.Recombinant covalently closed circular hepatitis B virus DNA induces prolonged viral persistence in immunocompetent mice[J].J Virol, 2014, 88 (14) :8045-8056.
    [44]ZHU YF, LI GY, CHANG H, et al.Preparing recombinant cccDNA of hepatitis B virus in vitro using minicircle DNA vector technogy[J].J Microbes Infect, 2017, 12 (4) :229-234. (in Chinese) 朱园飞, 李改云, 常豪, 等.应用微环DNA技术体外诱导和制备重组的乙型肝炎病毒共价闭合环状DNA[J].微生物与感染, 2017, 12 (4) :229-234.
    [45]YAN Z, ZENG J, YU Y, et al.HBVcircle:A novel tool to investigate hepatitis B virus covalently closed circular DNA[J].JHepatol, 2017, 66 (6) :1149-1157.
    [46]LI F, CHENG L, MURPHY CM, et al.Minicircle HBV cccDNAwith a Gaussia luciferase reporter for investigating HBV cccD-NA biology and developing cccDNA-targeting drugs[J].Sci Rep, 2016, (6) :36483.
    [47]RHIM JA, SANDGREN EP, PALMITER RD, et al.Complete reconstitution of mouse liver with xenogeneic hepatocytes[J].Proc Natl Acad Sci U S A, 1995, 92 (11) :4942-4946.
    [48]DANDRI M, BURDA MR, BURKLE A, et al.Increase in de novo HBV DNA integrations in response to oxidative DNA damage or inhibition of poly (ADP-ribosyl) ation[J].Hepatology, 2002, 35 (1) :217-223.
    [49]BISSIG KD, WIELAND SF, TRAN P, et al.Human liver chimeric mice provide a model for hepatitis B and C virus infection and treatment[J].J Clin Invest, 2010, 120 (3) :924-930.
    [50]VOLZ T, ALLWEISS L, BEN MM, et al.The entry inhibitor Myrcludex-B efficiently blocks intrahepatic virus spreading in humanized mice previously infected with hepatitis B virus[J].J Hepatol, 2013, 58 (5) :861-867.
    [51]ALLWEISS L, VOLZ T, GIERSCH K, et al.Proliferation of primary human hepatocytes and prevention of hepatitis B virus reinfection efficiently deplete nuclear cccDNA in vivo[J].Gut, 2018, 67 (3) :542-552.
    [52]YANG PL, ALTHAGE A, CHUNG J, et al.Hydrodynamic injection of viral DNA:A mouse model of acute hepatitis B virus infection[J].Proc Natl Acad Sci U S A, 2002, 99 (21) :13825-13830.
    [53]HUANG LR, WU HL, CHEN PJ, et al.An immunocompetent mouse model for the tolerance of human chronic hepatitis B virus infection[J].Proc Natl Acad Sci U S A, 2006, 103 (47) :17862-17867.
    [54]LI G, ZHU Y, SHAO D, et al.Recombinant covalently closed circular DNA of hepatitis B virus induces long-term viral persistence with chronic hepatitis in a mouse model[J].Hepatology, 2018, 67 (1) :56-70.
    [55]DONG XY, YUCHI J, WANG G, et al.Establishment of hepatitis B virus (HBV) chronic infection mouse model by in vivo transduction with a recombinant adeno-associated virus 8carrying 1.3 copies of HBV genome (r AAN8-1.3HBV) [J].Chin J Virol, 2010, 26 (6) :425-431. (in Chinese) 董小岩, 尉迟捷, 王刚, 等.高嗜肝性8型重组腺相关病毒体内转导法制备乙型肝炎病毒持续感染小鼠模型[J].病毒学报, 2010, 26 (6) :425-431.
    [56]DION S, BOURGINE M, GODON O, et al.Adeno-associated virus-mediated gene transfer leads to persistent hepatitis B virus replication in mice expressing HLA-A2 and HLA-DR1 molecules[J].J Virol, 2013, 87 (10) :5554-5563.
    [57]LUCIFORA J, PROTZER U.Attacking hepatitis B virus cccD-NA--The holy grail to hepatitis B cure[J].J Hepatol, 2016, 64 (1 Suppl) :s41-s48.
    [58]HUANG LR, GABEL YA, GRAF S, et al.Transfer of HBV genomes using low doses of adenovirus vectors leads to persistent infection in immune competent mice[J].Gastroenterology, 2012, 142 (7) :1447-1450, e1443.
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  • 收稿日期:  2019-04-04
  • 出版日期:  2019-06-20
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