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丙型肝炎病毒感染期间的宿主-病毒相互作用:一个复杂且动态的分子生物系统。

Host-virus interactions during hepatitis C virus infection: a complex and dynamic molecular biosystem.

作者信息

Pezacki John Paul, Singaravelu Ragunath, Lyn Rodney K

机构信息

Steacie Institute for Molecular Sciences, National Research Council of Canada, 100 Sussex Dr., Ottawa, Ontario, Canada.

出版信息

Mol Biosyst. 2010 Jul;6(7):1131-42. doi: 10.1039/b924668c.

Abstract

The hepatitis C virus (HCV) is a global health issue with no vaccine available and limited clinical treatment options. Like other obligate parasites, HCV requires host cellular components of an infected individual to propagate. These host-virus interactions during HCV infection are complex and dynamic and involve the hijacking of host cell environments, enzymes and pathways. Understanding this unique molecular biosystem has the potential to yield new and exciting strategies for therapeutic intervention. Advances in genomics and proteomics have opened up new possibilities for the rapid measurement of global changes at the transcriptional and translational levels during infection. However, these techniques only yield snapshots of host-virus interactions during HCV infection. Other new methods that involve the imaging of biomolecular interactions during HCV infection are required to identify key interactions that may be transient and dynamic. Herein we highlight systems biology based strategies that have helped to identify key host-virus interactions during HCV replication and infection. Novel biophysical tools are also highlighted for identification and visualization of activities and interactions between HCV and its host hepatocyte. As some of these methods mature, we expect them to pave the way forward for further exploration of this complex biosystem and elucidation of mechanisms for HCV pathogenesis and carcinogenesis.

摘要

丙型肝炎病毒(HCV)是一个全球性的健康问题,目前尚无可用疫苗,临床治疗选择也有限。与其他专性寄生虫一样,HCV需要受感染个体的宿主细胞成分来进行繁殖。HCV感染期间的这些宿主-病毒相互作用是复杂且动态的,涉及对宿主细胞环境、酶和信号通路的劫持。了解这种独特的分子生物系统有可能产生令人兴奋的新治疗干预策略。基因组学和蛋白质组学的进展为快速测量感染期间转录和翻译水平的整体变化开辟了新的可能性。然而,这些技术只能提供HCV感染期间宿主-病毒相互作用的瞬时图像。需要其他涉及HCV感染期间生物分子相互作用成像的新方法来识别可能是瞬时和动态的关键相互作用。在此,我们重点介绍基于系统生物学的策略,这些策略有助于识别HCV复制和感染期间的关键宿主-病毒相互作用。还重点介绍了用于识别和可视化HCV与其宿主肝细胞之间的活性和相互作用的新型生物物理工具。随着其中一些方法的成熟,我们期望它们为进一步探索这个复杂的生物系统以及阐明HCV发病机制和致癌机制铺平道路。

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