摘要
对驱动HCV完成生命周期的阶段和信号传递的理解取得的主要突破是在体外模型中完成的。这些模型促进了高病毒的产生,促成了参与病毒入侵,转译和复制的路径和因素的发现。HCV通过它的衣壳上的糖蛋白与细胞受体的结合进入宿主细胞,然后进行网格蛋白介导的胞吞作用和与细胞膜的融合,使得病毒脱壳进入细胞。这些连锁的活动是被不同共受体的介入调节的,例如SR-B1, CD81和紧密结合蛋白claudin和occludin。HCV的 RNA复制和转译是成对的过程,需要复制酶,解旋酶和其他带有细胞调整因子的病毒蛋白质的协同作用。病毒粒子的包装和释放是易被针对的阶段,但这需要更深入的研究。HCV的免疫反应相当无力,抑制E2-CD81绑定的中和抗体不能防止感染。细胞接触导致的HCV传播会造成慢性感染的发展。须要特别说明的是,CD81依赖性和参与进入细胞间感染的其他辅助因子的作用以及病毒从宿主中和反应中的逃脱犹待证实。为了说明涉及HCV感染的病毒和细胞机理,在这我们回顾了一些在了解了HCV宿主细胞的相互作用以后的,从病毒进入到释放出细胞的已取得的发现,这有助于定义新的分子靶点来提供抗病毒治疗策略。
关键词: HCV感染,免疫机制,生命周期和靶点,传播和繁殖,阶段和通路。
图形摘要
Current Drug Targets
Title:Steps and Routes of HCV Infection: The Great Promise of New Anti-Viral Targets
Volume: 16 Issue: 7
Author(s): Annalisa Crema, Antonio Ponzetto, Massimo Clementi and Guido Carloni
Affiliation:
关键词: HCV感染,免疫机制,生命周期和靶点,传播和繁殖,阶段和通路。
摘要: A major breakthrough in understanding the steps and signalling that drives the HCV to reach a full life-cycle has been achieved by in vitro models that have facilitated elevated virus production, resulting in the discovery of pathways and factors involved in virus entry, translation and replication. The HCV enters host cells through binding of its envelope glycoproteins to cell receptors, followed by clathrin-mediated endocytosis and fusion with cell membranes, leading to virus uncoating and cell entry. This chain of events is mediated by sequential involvement of different co-receptors, for example, SR-B1, CD81 and the tight-junction proteins- claudin and occludin. HCV RNA replication and translation are coupled processes, requiring cooperation of replicase, helicase and other viral proteins with cell-regulatory factors. Virion packaging and release are highly targetable steps, although they require greater in-depth investigation. The HCV-immune response appears to be fairly ineffective, and neutralizing antibodies that inhibit E2-CD81 binding are unable to resolve infection. HCV-transmission through cell-to-cell contact has been implicated in the evolution of chronic infection. In particular, CD81-dependency and the role of other co-factors involved in entry in cell-to-cell infection, as well as virus escape from host-neutralization still require confirmation. To highlight viral and cell mechanisms implicated in HCVinfection, we review here some of the major discoveries that have been made, from virus entry to its release from infected cells, in understanding the HCV host-cell interplay, which may help in defining new molecular targets to provide therapeutic antiviral strategies.
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Cite this article as:
Annalisa Crema, Antonio Ponzetto, Massimo Clementi and Guido Carloni , Steps and Routes of HCV Infection: The Great Promise of New Anti-Viral Targets, Current Drug Targets 2015; 16 (7) . https://dx.doi.org/10.2174/1389450116666150213111603
DOI https://dx.doi.org/10.2174/1389450116666150213111603 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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