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日本脑炎或西尼罗河病毒感染后人神经元模型蛋白质组的比较及蚊唾液在神经发病机制中的潜在作用。

Comparison of a human neuronal model proteome upon Japanese encephalitis or West Nile Virus infection and potential role of mosquito saliva in neuropathogenesis.

机构信息

Institut Pasteur, Environment and Infectious Risks Unit, Arbovirus Group, Paris, France.

Institut Pasteur, Plateforme Protéomique, Unité de Spectrométrie de Masse pour la Biologie (MSBio), Centre de Ressources et Recherches Technologiques (C2RT), USR CNRS, Paris, France.

出版信息

PLoS One. 2020 May 6;15(5):e0232585. doi: 10.1371/journal.pone.0232585. eCollection 2020.

Abstract

Neurotropic flavivirus Japanese encephalitis virus (JEV) and West Nile virus (WNV) are amongst the leading causes of encephalitis. Using label-free quantitative proteomics, we identified proteins differentially expressed upon JEV (gp-3, RP9) or WNV (IS98) infection of human neuroblastoma cells. Data are available via ProteomeXchange with identifier PXD016805. Both viruses were associated with the up-regulation of immune response (IFIT1/3/5, ISG15, OAS, STAT1, IRF9) and the down-regulation of SSBP2 and PAM, involved in gene expression and in neuropeptide amidation respectively. Proteins associated to membranes, involved in extracellular matrix organization and collagen metabolism represented major clusters down-regulated by JEV and WNV. Moreover, transcription regulation and mRNA processing clusters were also heavily regulated by both viruses. The proteome of neuroblastoma cells infected by JEV or WNV was significantly modulated in the presence of mosquito saliva, but distinct patterns were associated to each virus. Mosquito saliva favored modulation of proteins associated with gene regulation in JEV infected neuroblastoma cells while modulation of proteins associated with protein maturation, signal transduction and ion transporters was found in WNV infected neuroblastoma cells.

摘要

神经亲和性黄病毒乙型脑炎病毒(JEV)和西尼罗河病毒(WNV)是导致脑炎的主要原因之一。我们使用无标记定量蛋白质组学方法,鉴定了 JEV(gp-3、RP9)或 WNV(IS98)感染人神经母细胞瘤细胞后差异表达的蛋白质。数据可通过 ProteomeXchange 以标识符 PXD016805 获得。两种病毒都与免疫反应的上调(IFIT1/3/5、ISG15、OAS、STAT1、IRF9)和 SSBP2 和 PAM 的下调相关,分别涉及基因表达和神经肽酰胺化。与膜相关的、参与细胞外基质组织和胶原代谢的蛋白质代表了 JEV 和 WNV 下调的主要簇。此外,转录调控和 mRNA 加工簇也受到两种病毒的严重调控。在存在蚊子唾液的情况下,JEV 或 WNV 感染的神经母细胞瘤细胞的蛋白质组显著被调节,但与每种病毒相关的模式不同。蚊子唾液有利于 JEV 感染的神经母细胞瘤细胞中与基因调控相关的蛋白质的调节,而与蛋白质成熟、信号转导和离子转运相关的蛋白质的调节则存在于 WNV 感染的神经母细胞瘤细胞中。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/678a/7202638/88e2b96a2c42/pone.0232585.g001.jpg

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