MEK5/ERK5/mef2: A novel signaling pathway affected by hepatitis C virus non-enveloped capsid-like particles
MEK5/ERK5/mef2: A novel signaling pathway affected by hepatitis C virus non-enveloped capsid-like particles
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DOI：
10.1016/j.bbamcr.2011.06.015
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发表时间：
2011-10-01
影响因子：
5.1
通讯作者：
Georgopoulou, Urania
中科院分区：
文献类型：
--
作者：
Katsarou, Konstantina;Tsitoura, Panagiota;Georgopoulou, Urania
丙型肝炎病毒（HCV）是一种RNA正链病毒，属于黄病毒科.病毒颗粒由含有基因组的衣壳组成，被E1和E2蛋白包围，然而，已观察到不同形式的病毒颗粒，包括无包膜颗粒。以前的报告提出，丙型肝炎病毒无包膜capture-like颗粒（HCVne）进入肝细胞起源通过网格蛋白介导的内吞作用，在此期间发生不同的信号事件。在这份报告中，我们表明HCVne颗粒能够以剂量依赖性方式诱导最近发现的ERK 5通路。ERK 5通路可以被生长因子和其他细胞外信号激活。这种特异性激活通过一种充分表征的上游激酶发生。MEK 5，并且能够诱导mef 2的基因调节。相反，当HCV核心结构蛋白和NS 5A非结构蛋白内源性表达时，未检测到该途径的激活。这些细胞信号事件可能是至关重要的，并可能为阐明与HCV感染相关的细胞表现提供线索。(C)2011爱思唯尔有限公司版权所有。
Hepatitis C virus (HCV) is an RNA positive strand virus, member of the Flaviviridae family. The viral particle is composed of a capsid containing the genome, surrounded by E1 and E2 proteins, however different forms of viral particles have been observed including non-enveloped particles. Previous reports have proposed that hepatitis C non-enveloped capsid-like particles (HCVne) enter cells of hepatic origin via clathrin-mediated endocytosis, during which different signaling events occur. In this report we show that HCVne particles are capable of inducing the recently discovered ERK5 pathway, in a dose dependent way. The ERK5 pathway can be activated by growth factors and other extracellular signals. This specific activation occurs through a well characterized upstream kinase. MEK5, and is capable of inducing gene regulation of mef2. In contrast, when HCV core structural and NS5A non-structural proteins were expressed endogenously no activation of this pathway was detected. These cell signaling events could be of critical importance and might give clues for the elucidation of cellular manifestations associated with HCV infection. (C) 2011 Elsevier B.V. All rights reserved.