揭示乙肝病毒聚合酶在新抗病毒策略中的作用。
Unveiling the roles of HBV polymerase for new antiviral strategies.
作者信息
Clark Daniel N, Hu Jianming
机构信息
The Pennsylvania State University College of Medicine, Milton S Hershey Medical Center, PA 17033, USA.
出版信息
Future Virol. 2015;10(3):283-295. doi: 10.2217/fvl.14.113.
Abstract
Infection with HBV is common worldwide, with over 350 million chronic carriers. Chronic HBV infection is associated with cirrhosis and hepatocellular carcinoma. All currently available oral antivirals are directed against the HBV polymerase enzyme, a reverse transcriptase. HBV polymerase contains several important domains and motifs which define its functions and reveal ways to further target it. This enzyme executes many functions required for the HBV replication cycle, including viral RNA binding, RNA packaging, protein priming, template switching, DNA synthesis and RNA degradation. In addition, HBV polymerase must interact with host proteins for its functions. Future therapeutics may inhibit not only the DNA synthesis steps which are carried out by the reverse transcriptase domain (as all current antivirals do) but other domains, functions and interactions which are essential to the HBV replication cycle.
摘要
乙肝病毒（HBV）感染在全球范围内很常见，慢性携带者超过3.5亿人。慢性HBV感染与肝硬化和肝细胞癌相关。目前所有可用的口服抗病毒药物均针对HBV聚合酶，一种逆转录酶。HBV聚合酶包含几个重要的结构域和基序，这些结构域和基序决定了它的功能，并揭示了进一步靶向它的方法。这种酶执行HBV复制周期所需的许多功能，包括病毒RNA结合、RNA包装、蛋白质引发、模板转换、DNA合成和RNA降解。此外，HBV聚合酶必须与宿主蛋白相互作用以发挥其功能。未来的治疗方法可能不仅抑制由逆转录酶结构域执行的DNA合成步骤（如同所有目前的抗病毒药物那样），还抑制对HBV复制周期至关重要的其他结构域、功能和相互作用。
相似文献
1
Unveiling the roles of HBV polymerase for new antiviral strategies.揭示乙肝病毒聚合酶在新抗病毒策略中的作用。
Future Virol. 2015;10(3):283-295. doi: 10.2217/fvl.14.113.
2
Hepatitis B virus reverse transcriptase - Target of current antiviral therapy and future drug development.乙型肝炎病毒逆转录酶——当前抗病毒治疗的靶点与未来药物研发方向
Antiviral Res. 2015 Nov;123:132-7. doi: 10.1016/j.antiviral.2015.09.011. Epub 2015 Sep 25.
3
RNA-Binding Motif Protein 24 (RBM24) Is Involved in Pregenomic RNA Packaging by Mediating Interaction between Hepatitis B Virus Polymerase and the Epsilon Element.RNA 结合基序蛋白 24（RBM24）通过介导乙型肝炎病毒聚合酶与 ε 元件之间的相互作用参与前基因组 RNA 包装。
J Virol. 2019 Mar 5;93(6). doi: 10.1128/JVI.02161-18. Print 2019 Mar 15.
4
Hepatitis B virus reverse transcriptase: diverse functions as classical and emerging targets for antiviral intervention.乙型肝炎病毒逆转录酶：作为抗病毒干预的经典和新出现靶点的多种功能
Emerg Microbes Infect. 2013 Sep;2(9):e56. doi: 10.1038/emi.2013.56. Epub 2013 Sep 4.
5
Mapping of Functional Subdomains in the Terminal Protein Domain of Hepatitis B Virus Polymerase.乙肝病毒聚合酶末端蛋白结构域功能亚结构域的定位
J Virol. 2017 Jan 18;91(3). doi: 10.1128/JVI.01785-16. Print 2017 Feb 1.
6
Treatment for hepatitis B in patients with drug resistance.耐药性乙肝患者的治疗。
Ann Transl Med. 2016 Sep;4(18):334. doi: 10.21037/atm.2016.09.19.
7
Revisiting Hepatitis B Virus: Challenges of Curative Therapies.重新审视乙型肝炎病毒：治愈疗法的挑战。
J Virol. 2019 Sep 30;93(20). doi: 10.1128/JVI.01032-19. Print 2019 Oct 15.
8
Discovery and Mechanistic Study of Benzamide Derivatives That Modulate Hepatitis B Virus Capsid Assembly.调节乙型肝炎病毒衣壳组装的苯甲酰胺衍生物的发现与机制研究
J Virol. 2017 Jul 27;91(16). doi: 10.1128/JVI.00519-17. Print 2017 Aug 15.
9
Management of viral hepatitis B.乙型病毒性肝炎的管理
J Gastroenterol Hepatol. 2002 Feb;17 Suppl:S125-45. doi: 10.1046/j.1440-1746.17.s1.3.x.
10
T-cell therapy for chronic viral hepatitis.慢性病毒性肝炎的T细胞疗法。
Cytotherapy. 2017 Nov;19(11):1317-1324. doi: 10.1016/j.jcyt.2017.07.011. Epub 2017 Aug 25.
引用本文的文献
1
Viral infection, APOBEC3 dysregulation, and cancer.病毒感染、载脂蛋白B mRNA编辑酶催化多肽样3（APOBEC3）失调与癌症
Front Genet. 2024 Dec 23;15:1489324. doi: 10.3389/fgene.2024.1489324. eCollection 2024.
2
Generation of Replication-Competent Hepatitis B Virus Harboring Tagged Polymerase for Visualization and Quantification of the Infection.携带标记聚合酶的具有复制能力的乙型肝炎病毒的产生，用于感染的可视化和定量分析。
Microbiol Immunol. 2025 Jan;69(1):43-58. doi: 10.1111/1348-0421.13183. Epub 2024 Dec 2.
3
Regulation of Hepatitis B Virus Replication by Modulating Endoplasmic Reticulum Stress (ER-Stress).通过调节内质网应激（ER应激）来调控乙型肝炎病毒复制
Int J Microbiol. 2024 Aug 30;2024:9117453. doi: 10.1155/2024/9117453. eCollection 2024.
4
Deep mutational scanning of hepatitis B virus reveals a mechanism for cis-preferential reverse transcription.深度突变扫描揭示乙型肝炎病毒顺式偏好性逆转录的机制。
Cell. 2024 May 23;187(11):2735-2745.e12. doi: 10.1016/j.cell.2024.04.008. Epub 2024 May 8.
5
Full-Length Genome Sequencing and Analysis of Hepatitis B Viruses Isolated from Iraqi Patients.对从伊拉克患者中分离出的乙型肝炎病毒进行全基因组测序与分析。
Int J Microbiol. 2024 Apr 29;2024:6826495. doi: 10.1155/2024/6826495. eCollection 2024.
6
Polymorphisms predicting phylogeny in hepatitis B virus.预测乙型肝炎病毒系统发育的多态性
Virus Evol. 2022 Dec 10;9(1):veac116. doi: 10.1093/ve/veac116. eCollection 2023.
7
Spacer Domain in Hepatitis B Virus Polymerase: Plugging a Hole or Performing a Role?乙型肝炎病毒聚合酶中的间隔结构域：填补空缺还是发挥作用？
J Virol. 2022 May 11;96(9):e0005122. doi: 10.1128/jvi.00051-22. Epub 2022 Apr 12.
8
Multiomics Analysis of Endocytosis upon HBV Infection and Identification of SCAMP1 as a Novel Host Restriction Factor against HBV Replication.多组学分析 HBV 感染时的内吞作用，并鉴定 SCAMP1 作为一种新型宿主限制因子对抗 HBV 复制。
Int J Mol Sci. 2022 Feb 17;23(4):2211. doi: 10.3390/ijms23042211.
9
Identification and Characterization of Besifovir-Resistant Hepatitis B Virus Isolated from a Chronic Hepatitis B Patient.从一名慢性乙型肝炎患者中分离出的对贝西福韦耐药的乙型肝炎病毒的鉴定与特征分析。
Biomedicines. 2022 Jan 26;10(2):282. doi: 10.3390/biomedicines10020282.
10
Viral and cellular oncogenes promote immune evasion.病毒癌基因和细胞癌基因促进免疫逃逸。
Oncogene. 2022 Feb;41(7):921-929. doi: 10.1038/s41388-021-02145-1. Epub 2022 Jan 13.
本文引用的文献
1
Hepatitis B virus reverse transcriptase: diverse functions as classical and emerging targets for antiviral intervention.乙型肝炎病毒逆转录酶：作为抗病毒干预的经典和新出现靶点的多种功能
Emerg Microbes Infect. 2013 Sep;2(9):e56. doi: 10.1038/emi.2013.56. Epub 2013 Sep 4.
2
Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses.宿主DNA修复酶TDP2参与乙型肝炎病毒共价闭合环状DNA持久性储存库的形成。
Proc Natl Acad Sci U S A. 2014 Oct 7;111(40):E4244-53. doi: 10.1073/pnas.1409986111. Epub 2014 Sep 8.
3
Differential binding of tenofovir and adefovir to reverse transcriptase of hepatitis B virus.替诺福韦和阿德福韦与乙型肝炎病毒逆转录酶的差异结合
PLoS One. 2014 Sep 2;9(9):e106324. doi: 10.1371/journal.pone.0106324. eCollection 2014.
4
A randomized, open-label study comparing low-dose clevudine plus adefovir combination therapy with clevudine monotherapy in naïve chronic hepatitis B patients.一项在初治慢性乙型肝炎患者中比较低剂量克来夫定联合阿德福韦与克来夫定单药治疗的随机、开放标签研究。
Hepatol Int. 2014 May 25;8(3):375-81. doi: 10.1007/s12072-014-9537-5. eCollection 2014 Jul.
5
Prevention of hepatocellular carcinoma and its recurrence with anti-hepatitis B viral therapy.通过抗乙型肝炎病毒治疗预防肝细胞癌及其复发
Minerva Gastroenterol Dietol. 2014 Sep;60(3):191-200. Epub 2014 Jul 8.
6
Investigation into drug-resistant mutations of HBV from 845 nucleoside/nucleotide analogue-naive Chinese patients with chronic HBV infection.对845例初治慢性乙型肝炎病毒（HBV）感染中国患者的HBV耐药突变进行调查。
Antivir Ther. 2015;20(2):141-7. doi: 10.3851/IMP2813. Epub 2014 Jul 3.
7
No resistance to tenofovir disoproxil fumarate through 96 weeks of treatment in patients with lamivudine-resistant chronic hepatitis B.在拉米夫定耐药的慢性乙型肝炎患者中，经过 96 周的治疗，未发现对富马酸替诺福韦二吡呋酯产生耐药性。
Clin Gastroenterol Hepatol. 2014 Dec;12(12):2106-12.e1. doi: 10.1016/j.cgh.2014.05.024. Epub 2014 Jun 11.
8
Dasabuvir: A Non-Nucleoside Inhibitor of NS5B for the Treatment of Hepatitis C Virus Infection.达沙布韦：一种用于治疗丙型肝炎病毒感染的NS5B非核苷抑制剂。
Rev Recent Clin Trials. 2014;9(2):115-23. doi: 10.2174/1574887109666140529222602.
9
Management of chronic hepatitis B infection: current treatment guidelines, challenges, and new developments.慢性乙型肝炎感染的管理：当前治疗指南、挑战及新进展
World J Gastroenterol. 2014 May 28;20(20):6262-78. doi: 10.3748/wjg.v20.i20.6262.
10
Hepatitis B virus replication is blocked by a 2-hydroxyisoquinoline-1,3(2H,4H)-dione (HID) inhibitor of the viral ribonuclease H activity.乙型肝炎病毒复制被一种抑制病毒核糖核酸酶H活性的2-羟基异喹啉-1,3(2H,4H)-二酮（HID）所阻断。
Antiviral Res. 2014 Aug;108:48-55. doi: 10.1016/j.antiviral.2014.05.007. Epub 2014 May 20.
Zotero 插件