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丙型肝炎病毒细胞培养模型:为治疗发展铺平道路的基础研究赞歌。

Hepatitis C virus cell culture models: an encomium on basic research paving the road to therapy development.

作者信息

Lohmann Volker

机构信息

Department of Infectious Diseases, Molecular Virology, Centre for Integrative Infectious Disease Research (CIID), University of Heidelberg, INF 344, 1st Floor, 69120, Heidelberg, Germany.

出版信息

Med Microbiol Immunol. 2019 Feb;208(1):3-24. doi: 10.1007/s00430-018-0566-x. Epub 2018 Oct 8.

DOI:10.1007/s00430-018-0566-x
PMID:30298360
Abstract

Chronic hepatitis C virus (HCV) infections affect 71 million people worldwide, often resulting in severe liver damage. Since 2014 highly efficient therapies based on directly acting antivirals (DAAs) are available, offering cure rates of almost 100%, if the infection is diagnosed in time. It took more than a decade to discover HCV in 1989 and another decade to establish a cell culture model. This review provides a personal view on the importance of HCV cell culture models, particularly the replicon system, in the process of therapy development, from drug screening to understanding of mode of action and resistance, with a special emphasis on the contributions of Ralf Bartenschlager's group. It summarizes the tremendous efforts of scientists in academia and industry required to achieve efficient DAAs, focusing on the main targets, protease, polymerase and NS5A. It furthermore underpins the importance of strong basic research laying the ground for translational medicine.

摘要

慢性丙型肝炎病毒(HCV)感染影响着全球7100万人,常常导致严重的肝脏损伤。自2014年以来,基于直接作用抗病毒药物(DAA)的高效疗法问世,如果能及时诊断感染,治愈率几乎可达100%。1989年发现HCV用了十多年时间,又过了十年才建立起细胞培养模型。本综述就HCV细胞培养模型,尤其是复制子系统,在从药物筛选到作用机制及耐药性理解的治疗开发过程中的重要性发表个人观点,特别强调了拉尔夫·巴滕施拉格团队的贡献。它总结了学术界和工业界科学家为实现高效DAA所付出的巨大努力,重点关注主要靶点蛋白酶、聚合酶和NS5A。此外,它还强调了为转化医学奠定基础的强大基础研究的重要性。

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