Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance

Zika Virus Infection Disrupts Astrocytic Proteins Involved in Synapse Control and Axon Guidance
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DOI:
10.3389/fmicb.2019.00596
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发表时间:
2019-03-26
影响因子:
5.2
通讯作者:
Coombs, Kevin M.
Coombs, Kevin M.
中科院分区:
生物学2区
文献类型:
--
作者:
Sher, Affan A.;Glover, Kathleen K. M.;Coombs, Kevin M.

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第一次人类寨卡病毒(ZIKV)疫情于2007年在密克罗尼西亚报告,随后于2015年在巴西报告。最近的研究报告了欧洲、大洋洲和拉丁美洲的病例。2016年,美国也报告了ZIKV传播,世界卫生组织宣布其为国际关注的突发公共卫生事件。由于各种神经病症与ZIKV相关,例如小头畸形、格林-巴利综合征和中枢和外周神经系统的其他病症,包括脑病、(脑膜)脑炎和脊髓灰质炎,并且由于缺乏可靠的患者诊断,许多正在进行的研究试图了解ZIKV发病机制的分子机制。星形胶质细胞是中枢神经系统中最丰富的细胞之一。它们控制轴突引导、突触信号传导、神经递质运输和神经元的维持,并且被ZIKV靶向。在这项研究中,我们使用了一种新开发的多重适体技术(SOMAScan)来检查超过1300种人类星形胶质细胞蛋白。我们鉴定了近300种由ZIKV感染显著失调的星形胶质细胞蛋白,这些蛋白跨越不同的功能和信号通路,包括蛋白翻译、突触控制、细胞迁移和分化。
The first human Zika virus (ZIKV) outbreak was reported in Micronesia in 2007, followed by one in Brazil in 2015. Recent studies have reported cases in Europe, Oceania and Latin America. In 2016, ZIKV transmission was also reported in the US and the World Health Organization declared it a Public Health Emergency of International Concern. Because various neurological conditions are associated with ZIKV, such as microcephaly, Guillain-Barre syndrome, and other disorders of both the central and peripheral nervous systems, including encephalopathy, (meningo) encephalitis and myelitis, and because of the lack of reliable patient diagnosis, numerous ongoing studies seek to understand molecular mechanisms underlying ZIKV pathogenesis. Astrocytes are one of the most abundant cells in the CNS. They control axonal guidance, synaptic signaling, neurotransmitter trafficking and maintenance of neurons, and are targeted by ZIKV. In this study, we used a newly developed multiplexed aptamer-based technique (SOMAScan) to examine > 1300 human astrocyte cell proteins. We identified almost 300 astrocyte proteins significantly dysregulated by ZIKV infection that span diverse functions and signaling pathways, including protein translation, synaptic control, cell migration and differentiation.