JBC:IFITM家族蛋白抵抗HCV感染

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阿德莱德大学的研究人员已经发现了一个基因组的作用，它们可以抑制丙型肝炎病毒（HCV）在肝脏中发生感染。

这项发现发表在《生物化学杂志》上，阐明了这些基因的活性，以及它们是如何对病毒产生天然免疫反应的。

在澳大利亚HCV是一个主要的健康问题，大约有233，000人通过污染血液传播致病。未能检测到的HCV感染可导致慢性疾病和肝癌，这两种疾病的发生率都在增加。

研究表明，抗病毒蛋白（IFITM蛋白）在通过天然免疫反应产生的第一时间就能阻断HCV进入细胞。

“我们现在很好地认识了IFITM蛋白在肝细胞中的作用以及它们是如何抑制HCV感染的，”生物科学学院病毒发病机制实验室主任Michael Beard副教授说道。

“这使我们对HCV感染的宿主反应和HCV侵入过程有了更好地理解，从而为治疗方案的发展提供新的方向，以提高这种天然免疫反应，或特异性针对病毒产生模仿体。”

之前在实验室环境下已经证实，IFITM1，IFITM2和IFITM3蛋白对多种不同的病毒，包括HCV，有抗病毒作用。但迄今为止，蛋白在抑制HCV感染方面的实际作用仍然是一个谜。

Beard副教授和博士生Sumudu Narayana研究了在肝细胞内蛋白对HCV感染的影响。“Sumudu已经发现，表达高水平IFITM蛋白的肝细胞通过阻止病毒进入细胞来抵抗HCV感染，”Beard副教授说道。

“我们的研究小组证实了细胞内蛋白和HCV进入过程之间有特殊的相互作用。看起来蛋白是通过一种特殊方式共同作用来抵抗病毒的。同时为现在的治疗指出方向，通过加强这些机制，以防止病毒感染。”

来源：医脉通

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The Interferon-induced Transmembrane Proteins, IFITM1, IFITM2, and IFITM3 Inhibit Hepatitis C Virus Entry*

Sumudu K. Narayana‡,§,¶, Karla J. Helbig‡,§,¶, Erin M. McCartney‡,§,¶, Nicholas S. Eyre‡,§,¶, Rowena A. Bull‖, Auda Eltahla‖, Andrew R. Lloyd‖ and Michael R. Beard‡,§,¶1

The interferon-induced transmembrane (IFITM) family of proteins have recently been identified as important host effector molecules of the type I interferon response against viruses. IFITM1 has been identified as a potent antiviral effector against hepatitis C virus (HCV), whereas the related family members IFITM2 and IFITM3 have been described to have antiviral effects against a broad range of RNA viruses. Here, we demonstrate that IFITM2 and IFITM3 play an integral role in the interferon response against HCV and act at the level of late entry stages of HCV infection. We have established that in hepatocytes, IFITM2 and IFITM3 localize to the late and early endosomes, respectively, as well as the lysosome. Furthermore, we have demonstrated that S-palmitoylation of all three IFITM proteins is essential for anti-HCV activity, whereas the conserved tyrosine residue in the N-terminal domain of IFITM2 and IFITM3 plays a significant role in protein localization. However, this tyrosine was found to be dispensable for anti-HCV activity, with mutation of the tyrosine resulting in an IFITM1-like phenotype with the retention of anti-HCV activity and co-localization of IFITM2 and IFITM3 with CD81. In conclusion, we propose that the IFITM proteins act in a coordinated manner to restrict HCV infection by targeting the endocytosed HCV virion for lysosomal degradation and demonstrate that the actions of the IFITM proteins are indeed virus and cell-type specific.

http://intl.jbc.org/content/290/ ... 7-adac-3a1a286e5fb2