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标题: Science Signaling:丙型肝炎病毒是如何挫败免疫系统的 [打印本页]

作者: ipsvirus 时间: 2015-11-18 10:15
标题: Science Signaling:丙型肝炎病毒是如何挫败免疫系统的

一项新的研究揭示了丙型肝炎病毒（HCV）的一种蛋白在帮助该病毒躲避免疫系统以长期感染宿主机体的活动中所扮演的角色。这些发现开启了以这种病毒蛋白作为标靶治疗慢性丙型肝炎感染的可能性。

丙型肝炎是一种因HCV感染而引起的肝脏疾病，它会导致肝癌、肝功能衰竭、或肝硬化（疤痕组织的形成）。长期受到感染的患者的血中会有高浓度的TNF-α，这是一种信号分子，它能激活促炎的NF-κB通路，它是抗病毒免疫防御中的一个关键的组成部分。然而，尽管有高浓度的TNF-α，但这些病人仍然无法清除HCV的感染，表明该病毒能挫败先天性免疫反应。通过研究被HCV感染的人类肝细胞系，Yongzhi Chen 和同事发现了一种名叫NS3的蛋白病毒，它可能是HCV逃避免疫防御策略的基本元凶。

NS3可通过与一个叫做LUBAC的化合物结合而阻止NF-κB通路的激活，如果该化合物未被结合，它就会附着于NEMO上，而后者是激活NF-κB所需的调控分子。复制中的HCVs会产生大量的NS3蛋白，而这些蛋白会和NEMO竞争与LUBAC的结合，从而中断了NF-κB通路的这一关键性激活步骤。这些发现表明，阻断NS3或能为治疗慢性丙型肝炎感染提供一种可能的策略。

来源：生物360

作者: ipsvirus 时间: 2015-11-18 10:15
The hepatitis C virus protein NS3 suppresses TNF-α–stimulated activation of NF-κB by targeting LUBAC

Yongzhi Chen1,2, Liang He1,2, Yanan Peng1,2, Xiaodong Shi1, Jizheng Chen3, Jin Zhong4, Xinwen Chen3, Genhong Cheng1,5,*, and Hongyu Deng1,*

The transcription factor nuclear factor κB (NF-κB) is crucial for innate immune defense against viral infections, and its activation requires the ubiquitylation of upstream proteins, including the adaptor protein NEMO (NF-κB essential modulator). Many infectious pathogens, including hepatitis C virus (HCV), inhibit NF-κB signaling in host cells, which promotes pathogen survival. Frequently, HCV-infected individuals develop a chronic infection, which suggests that HCV can subvert host antiviral responses. We found that HCV infection and replication inhibited the activation of NF-κB by the inflammatory cytokine tumor necrosis factor–α (TNF-α), which was mediated by the viral protein NS3 and, to a lesser extent, NS5B. NS3 directly interacted with linear ubiquitin chain assembly complex (LUBAC), competed with NEMO for binding to LUBAC, and inhibited the LUBAC-mediated linear ubiquitylation of NEMO and the subsequent activation of NF-κB. Together, our results highlight an immune evasion strategy adopted by HCV to modulate host antiviral responses and enhance virus survival and persistence.

http://stke.sciencemag.org/conte ... 9-a20b-4b76e89a2f38

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