PDF(Pubmed)
Abstract：
Chikungunya virus (CHIKV) is a re-emerging mosquito-transmitted RNA virus causing joint and muscle pain. To better understand how CHIKV rewires the host cell and usurps host cell functions, we generated a systematic CHIKV-human protein-protein interaction map and revealed several novel connections that will inform further mechanistic studies. One of these novel interactions, between the viral protein E1 and STIP1 homology and U-box containing protein 1 (STUB1), was found to mediate ubiquitination of E1 and degrade E1 through the proteasome. Capsid associated with G3BP1, G3BP2 and AAA+ ATPase valosin-containing protein (VCP). Furthermore, VCP inhibitors blocked CHIKV infection, suggesting VCP could serve as a therapeutic target. Further work is required to fully understand the functional consequences of these interactions. Given that CHIKV proteins are conserved across alphaviruses, many virus-host protein-protein interactions identified in this study might also exist in other alphaviruses. Construction of interactome of CHIKV provides the basis for further studying the function of alphavirus biology.
摘要：
基孔肯雅病毒（CHIKV）是一种重新出现的蚊子传播的RNA病毒，引起关节和肌肉疼痛。为了更好地了解CHIKV如何重新连接宿主细胞并篡夺宿主细胞的功能，我们生成了系统的CHIKV-人蛋白质-蛋白质相互作用图谱,并揭示了几个新的连接,这将为进一步的机理研究提供依据.这些新颖的互动之一，病毒蛋白E1和STIP1同源性与含U盒蛋白1（STUB1）之间，发现介导E1的泛素化并通过蛋白酶体降解E1。衣壳与G3BP1、G3BP2和AAA+ATPase含valosin蛋白(VCP)相关。此外，VCP抑制剂阻断CHIKV感染，提示VCP可以作为治疗靶点。需要进一步的工作来充分理解这些相互作用的功能后果。鉴于CHIKV蛋白在甲病毒中是保守的，本研究中发现的许多病毒-宿主蛋白-蛋白相互作用也可能存在于其他甲病毒中.CHIKV相互作用组的构建为进一步研究甲病毒生物学功能奠定了基础。
