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Cell Research:中科院建立世界首个丙型肝炎病毒持续感染的动物模型

来源:生物谷 2014-08-30 13:12

2014年8月30日讯 /生物谷BIOON/ --中国科学院武汉病毒所和生物物理所研究人员在《Cell Research》上发表封面文章,报道了世界上首个反映HCV感染自然史和慢性病毒性肝炎进展的动物模型。自从40年前美国NIH研究人员首次发现丙型肝炎后,全球目前已经有约2亿人感染或携带HCV,我国则有超过4000万患者。丙肝可以导致肝硬化和肝癌等可怕后果,同时也给世界各国医疗卫生体系带来巨大压力。

由于HCV变异性极强,很容易产生抗药性。在过去很长时间中,许多科学家都在探索一种合适的动物模型以用作HCV的深入研究。然而HCV只感染人类和黑猩猩,因此开发这种实验小鼠模型在实践上遇到了极大困难。本研究主要是由中科院病毒所和生物物理所的陈新文和唐宏等人完成,他们表示这一研究的成功为揭示丙肝的致病机制提供了迄今最先进的材料,还能从根本上推动丙肝防治的疫苗和药物研究。研究人员在小鼠肝脏细胞上通过转基因技术表达了HCV进入肝细胞的两个受体分子,CD81和OCLN。HCV能够识别并侵入小鼠的肝脏细胞并进行高度复制。同时80%受感染的小鼠在随后都出现了典型的HCV急性感染和慢性病理进展,包括出现脂肪肝、肝纤维化和肝硬化等症状。目前该实验室的研究人员已经利用这一模型观察到HCV如何逃逸免疫系统以及抗病毒药物是如何降低病毒滴度的。(生物谷Bioon.com)

生物谷推荐的英文摘要:

Cell Research     

doi: 10.1038/cr.2014.116

Persistent hepatitis C virus infections and hepatopathological manifestations in immune-competent humanized mice

Jizheng Chen, Yang Zhao, Chao Zhang, Hairong Chen, Jin Feng, Xiumei Chi, Yu Pan, Jun Du, Min Guo, Huang Cao, Honghe Chen, Zilong Wang, Rongjuan Pei, Qian Wang, Lei Pan, Junqi Niu, Xinwen Chen and Hong Tang

The majority of hepatitis C virus (HCV) infection develops chronic infection, which causes steatosis, cirrhosis and hepatocellular carcinoma. However, understanding HCV chronicity and pathogenesis is hampered by its narrow host range, mostly restricted to human and chimpanzee. Recent endeavour to infect a variety of humanized mice has not been able to achieve persistent HCV infection unless the essential innate immune responsive genes are knocked out. Nevertheless, such immune-compromised humanized mice still lacked HCV infection-induced hepatopathogenesis. Here we report that transgenic mice in ICR background harboring both human CD81 and occludin genes (C/OTg) are permissive to HCV infection at a chronicity rate comparable to humans. In this mouse model, HCV accomplishes its replication cycle, leading to sustained viremia and infectivity for more than 12 months post infection with expected fibrotic and cirrhotic progression. Host factors favorable for HCV replication, and inadequate innate immune-response may contribute to the persistence. Lastly, NS3/4 protease inhibitor telaprevir can effectively inhibit de novo RNA synthesis and acute HCV infection of C/OTg mice. Thus, chronic HCV infection with complete replication cycle and hepatopathologic manifestations is recapitulated, for the first time, in immune-competent mice. This model will open a new venue to study the mechanisms of chronic hepatitis C and develop better treatments.

 

 

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