Lempp Florian A, Urban Stephan
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
German Centre for Infection Research (DZIF), Partner Site Heidelberg, 69120 Heidelberg, Germany.
Viruses. 2017 Jul 4;9(7):172. doi: 10.3390/v9070172.
The human Hepatitis Delta Virus (HDV) is unique among all viral pathogens. Encoding only one protein (Hepatitis Delta Antigen; HDAg) within its viroid-like self-complementary RNA, HDV constitutes the smallest known virus in the animal kingdom. To disseminate in its host, HDV depends on a helper virus, the human Hepatitis B virus (HBV), which provides the envelope proteins required for HDV assembly. HDV affects an estimated 15-20 million out of the 240 million chronic HBV-carriers and disperses unequally in disparate geographical regions of the world. The disease it causes (chronic Hepatitis D) presents as the most severe form of viral hepatitis, leading to accelerated progression of liver dysfunction including cirrhosis and hepatocellular carcinoma and a high mortality rate. The lack of approved drugs interfering with specific steps of HDV replication poses a high burden for gaining insights into the molecular biology of the virus and, consequently, the development of specific novel medications that resiliently control HDV replication or, in the best case, functionally cure HDV infection or HBV/HDV co-infection. This review summarizes our current knowledge of HBV molecular biology, presents an update on novel cell culture and animal models to study the virus and provides updates on the clinical development of the three developmental drugs Lonafarnib, REP2139-Ca and Myrcludex B.
人类丁型肝炎病毒（HDV）在所有病毒病原体中独树一帜。HDV在其类病毒样自我互补RNA中仅编码一种蛋白质（丁型肝炎抗原；HDAg），是动物界已知最小的病毒。为了在宿主中传播，HDV依赖于一种辅助病毒——人类乙型肝炎病毒（HBV），后者提供HDV组装所需的包膜蛋白。在2.4亿慢性HBV携带者中，估计有1500万至2000万人受到HDV影响，且在世界不同地理区域的分布不均。它所引发的疾病（慢性丁型肝炎）是最严重的病毒性肝炎形式，会导致肝功能障碍加速发展，包括肝硬化和肝细胞癌，并伴有高死亡率。由于缺乏能干扰HDV复制特定步骤的获批药物，深入了解该病毒的分子生物学以及开发能有效控制HDV复制、最好能功能性治愈HDV感染或HBV/HDV合并感染的新型特效药物面临着巨大挑战。本综述总结了我们目前对HDV分子生物学的认识，介绍了用于研究该病毒的新型细胞培养和动物模型的最新情况，并提供了三种研发药物（洛那法尼、REP2139-Ca和Myrcludex B）临床开发的最新进展。
