乙肝病毒核心蛋白的结构及其去功能化在乙肝抗病毒治疗中的应用

中国临床药理学与治疗学 ›› 2010, Vol. 15 ›› Issue (10): 1170-1173.

乙肝病毒核心蛋白的结构及其去功能化在乙肝抗病毒治疗中的应用

刘雪妮, 潘庆春, 臧国庆, 余永胜

上海交通大学附属第六人民医院感染科,上海 200233

收稿日期:2010-08-20 修回日期:2010-10-12 发布日期:2020-09-16
通讯作者: 余永胜,男,主任医师,硕导,研究方向:病毒性肝炎。E-mail: yuyongsheng@medmail.com.cn
作者简介:刘雪妮,女,硕士研究生,研究方向:病毒性肝炎。Tel: 15800853235 E-mail: zsk370@163.com.cn
基金资助:
国家自然科学基金(81070335);上海市自然科学基金项目(08ZR1411500)

Structure of hepatitis B virus core protein and disablement in the hepatitis B antiviral therapy

LIU Xue-ni, PAN Qing-chun, ZANG Guo-qing, YU Yong-sheng

Department of Infectious Diseases, Shanghai Sixth People Hospital, Shanghai JiaoTong University, Shanghai 200233, China

Received:2010-08-20 Revised:2010-10-12 Published:2020-09-16

摘要/Abstract

摘要： 核心蛋白由乙型肝炎病毒(HBV)c基因编码,可包被前基因组mRNA形成核衣壳,在HBV复制中发挥着关键作用。通过如RNA干扰、抗核心蛋白抗体及构建核心蛋白突变体等方式实现其去功能化,可阻断核衣壳形成,达到抑制HBV复制的目的,可作为乙肝抗病毒治疗的一个新靶点。

关键词: 乙型肝炎病毒, 核心蛋白, 核壳体, 去功能化

Abstract: Core protein which is encoded by the hepatitis B virus (HBV) c gene can package the pre-genome mRNA to form nucleocapsid and play a key role in the HBV replication. The disablement of core protein by RNA interference, core protein antibody and core protein mutant can block capsid formation, inhibit HBV replication. This can be used as a new target for hepatitis B antiviral therapy.

Key words: Hepatitis B virus, Core protein, Nucleocapsid, Disablement

中图分类号:

R512.6

刘雪妮, 潘庆春, 臧国庆, 余永胜. 乙肝病毒核心蛋白的结构及其去功能化在乙肝抗病毒治疗中的应用[J]. 中国临床药理学与治疗学, 2010, 15(10): 1170-1173.

LIU Xue-ni, PAN Qing-chun, ZANG Guo-qing, YU Yong-sheng. Structure of hepatitis B virus core protein and disablement in the hepatitis B antiviral therapy[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2010, 15(10): 1170-1173.

参考文献

[1] Garcia ML, Byfield R, Robek MD. Hepatitis B virus replication and release are independent of core lysine ubiquitination[J]. J Virol, 2009,83(10):4923-4933.
[2] He XX, Lin JS, Chang Y, et al. Effects of two novel nucleoside analogues on different hepatitis B virus promoters[J]. World J Gastroenterol, 2008,14(12):1836-1841.
[3] Choi IG, Yu YG. Interaction and assembly of HBV structural proteins: novel target sites of anti-HBV agents[J]. Infect Disord Drug Targets, 2007,7(3):251-256.
[4] Scaglioni PP, Melegari M, Wands JR. Posttranscriptional regulation of hepatitis B virus replication by the precore protein[J]. J Virol, 1997,71(1):345-353.
[5] Bruss V. Envelopment of the hepatitis B virus nucleocapsid[J]. Virus Res, 2004,106(2):199-209.
[6] Pairan A, Bruss V. Functional surfaces of the hepatitis B virus capsid[J]. J Virol, 2009,83(22):11616-11623.
[7] Bruss V.Hepatitis B virus morphogenesis[J].World J Gastroenterol, 2007,13(1):65-73.
[8] Hilmer JK, Zlotnick A, Bothner B. Conformational equilibria and rates of localized motion within hepatitis B virus capsids[J]. J Mol Biol, 2008,375(2):581-594.
[9] Günther S, Piwon N, Jung A,et al. Enhanced replication contributes to enrichment of hepatitis B virus with a deletion in the core gene[J]. Virology, 2000,273(2):286-299.
[10] Ying RS, Zhu C, Fan XG, et al. Hepatitis B virus is inhibited by RNA interference in cell culture and in mice[J]. Antiviral Res, 2007,73(1):24-30.
[11] Shlomai A, Shaul Y. Inhibition of hepatitis B virus expression and replication by RNA interference[J]. Hepatology, 2003,37(4):764-770.
[12] 余永胜,陈有华.抗乙型肝炎病毒基因治疗的若干进展[J].中国临床药理学与治疗学,2002,7(6):574-576.
[13] Luk JM, Wong KF. Monoclonal antibodies as targeting and therapeutic agents: prospects for liver transplantation, hepatitis and hepatocellular carcinoma[J]. Clin Exp Pharmacol Physiol, 2006,33(5/6):482-488.
[14] Filpula D. Antibody engineering and modification technologies[J]. Biomol Eng, 2007,24(2):201-215.
[15] 邸雅南,胡大荣,胡学玲. HBV C基因截短型突变体抗HBV作用研究[J].中华传染病学杂志,2005,23(5):293-296.
[16] Zlotnick A, Ceres P, Singh S, et al. A small molecule inhibits and misdirects assembly of hepatitis B virus capsids[J]. J Virol, 2002,76(10):4848-4854.
[17] Deres K, Schröder CH, Paessens A, et al. Inhibition of hepatitis B virus replication by drug-induced depletion of nuclecocapsids[J]. Science, 2003, 299(5608):893-896.