丁型肝炎病毒：洞察一个奇特的病原体和新的治疗方案

StephenW

Hepatitis delta virus: insights into a peculiar pathogen and novel treatment options

    Florian A. Lempp,    Yi Ni    & Stephan Urban   

Affiliations

    Department of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
        Florian A. Lempp, Yi Ni & Stephan Urban
    German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 324, 69120 Heidelberg, Germany.
        Yi Ni & Stephan Urban


   
    Nature Reviews Gastroenterology & Hepatology
    13,
    580–589
    (2016)
    doi:10.1038/nrgastro.2016.126

Published online
    18 August 2016


Abstract



Chronic hepatitis D is the most severe form of viral hepatitis, affecting ~20 million HBV-infected people worldwide. The causative agent, hepatitis delta virus (HDV), is a unique human pathogen: it is the smallest known virus; it depends on HBV to disseminate its viroid-like RNA; it encodes only one protein (HDAg), which has both structural and regulatory functions; and it replicates using predominantly host proteins. The failure of HBV-specific nucleoside analogues to suppress the HBV helper function, and the limitations of experimental systems to study the HDV life cycle, have impeded the development of HDV-specific drugs. Thus, the only clinical regimen for HDV is IFNα, which shows some efficacy but long-term virological responses are rare. Insights into the receptor-mediated entry of HDV, and the observation that HDV assembly requires farnesyltransferase, have enabled novel therapeutic strategies to be developed. Interference with entry, for example through blockade of the HBV–HDV-specific receptor sodium/taurocholate cotransporting polypeptide NTCP by Myrcludex B, and inhibition of assembly by blockade of farnesyltransferase using lonafarnib or nucleic acid polymers such as REP 2139-Ca, have shown promising results in phase II studies. In this Review, we summarize our knowledge of HDV epidemiology, pathogenesis and molecular biology, with a particular emphasis on possible future developments.

StephenW

丁型肝炎病毒：洞察一个奇特的病原体和新的治疗方案

    弗洛里安A. Lempp，漪妮和斯蒂芬城市

隶属关系

    传染科，分子病毒学，大学医院海德堡，林Neuenheimer费尔德345，6912​​0德国海德堡。
        弗洛里安A. Lempp，漪妮和斯蒂芬城市
    德国中心感染研究（DZIF），海德堡合作网站进出口Neuenheimer费尔德324，6912​​0德国海德堡。
        漪妮和斯蒂芬城市


   
    自然评论：消化内科肝病
    13，
    580-589
    （2016年）
    DOI：10.1038 / nrgastro.2016.126

网上公布
    2016年8月18日


抽象



慢性丁型肝炎是病毒性肝炎的最严重的形式，影响全球〜2000万乙肝病毒感染者。致病因子，丁型肝炎病毒（HDV），是一个独特的人病原体：它是最小的已知病毒;这取决于HBV传播其类病毒样RNA;它仅编码一种蛋白质（HDAg的），其具有的结构和调节功能;它使用复制主要宿主蛋白。 HBV特异性核苷类似物的失败来抑制HBV的辅助功能，实验系统的局限性，研究HDV生命周期，阻碍了具体的HDV-药物的开发。因此，唯一的临床治疗方案的HDV是IFNα，这显示了一些疗效，但长期的病毒学反应是罕见的。洞察HDV的受体介导的条目，而HDV装配要求法尼基观察，已经启用了待开发新的治疗策略。干扰项，例如通过HBV-HDV特异性受体钠/牛磺胆由Myrcludex乙cotransporting多肽NTCP的封锁，与组装的抑制法尼基转移酶使用lonafarnib或核酸聚合物如REP 2139钙的封锁，已显示有希望的结果II期研究。在这次审查中，我们总结了我们的HDV流行病学，发病机制和分子生物学方面的知识，并特别强调对未来可能的发展