Department of Medical Microbiology & Infectious Diseases, University of Manitoba, Winnipeg, MB R3E 0J9, Canada.
Manitoba Centre for Proteomics & Systems Biology, University of Manitoba, Winnipeg, MB R3E 3P4, Canada.
Viruses. 2022 Dec 29;15(1):97. doi: 10.3390/v15010097.
(1) Background: Zika virus (ZIKV), an arbo-flavivirus, is transmitted via mosquitoes Following its major outbreaks in 2013, 2014 and 2016, WHO declared it a Public Health Emergency of International Concern. Symptoms of ZIKV infection include acute fever, conjunctivitis, headache, muscle & joint pain and malaise. Cases of its transmission also have been reported via perinatal, sexual and transfusion transmission. ZIKV pathologies include meningo-encephalitis and myelitis in the central nervous system (CNS) and Guillain-Barré syndrome and acute transient polyneuritis in the peripheral nervous system (PNS). Drugs like azithromycin have been tested as inhibitors of ZIKV infection but no vaccines or treatments are currently available. Astrocytes are the most abundant cells in the CNS and among the first cells in CNS infected by ZIKV; (2) Methods: We previously used SOMAScan proteomics to study ZIKV-infected astrocytic cells. Here, we use mass spectrometric analyses to further explain dysregulations in the cellular expression profile of glioblastoma astrocytoma U251 cells. We also knocked down (KD) some of the U251 cellular proteins using siRNAs and observed the impact on ZIKV replication and infectivity; (3) Results & Conclusions: The top ZIKV dysregulated cellular networks were antimicrobial response, cell death, and energy production while top dysregulated functions were antigen presentation, viral replication and cytopathic impact. Th1 and interferon signaling pathways were among the top dysregulated canonical pathways. siRNA-mediated KD of HLA-A, IGFBP5, PSMA2 and HSPA5 increased ZIKV titers and protein synthesis, indicating they are ZIKV restriction factors. ZIKV infection also restored HLA-A expression in HLA-A KD cells by 48 h post-infection, suggesting interactions between this gene product and ZIKV.
(1) 背景：寨卡病毒（ZIKV）是一种虫媒黄病毒，通过蚊子传播。自 2013 年、2014 年和 2016 年的重大疫情爆发以来，世界卫生组织宣布其为国际关注的突发公共卫生事件。寨卡病毒感染的症状包括急性发热、结膜炎、头痛、肌肉和关节疼痛以及不适。也有报道称，寨卡病毒通过围产期、性和输血传播。寨卡病毒病包括中枢神经系统（CNS）的脑膜脑炎和脊髓炎以及周围神经系统（PNS）的格林-巴利综合征和急性短暂性多发性神经炎。已经测试了像阿奇霉素这样的药物作为寨卡病毒感染的抑制剂，但目前没有疫苗或治疗方法。星形胶质细胞是中枢神经系统中最丰富的细胞，也是中枢神经系统中最早感染寨卡病毒的细胞之一；
(2) 方法：我们之前使用 SOMAScan 蛋白质组学来研究感染寨卡病毒的星形胶质细胞。在这里，我们使用质谱分析进一步解释神经胶质瘤星形细胞瘤 U251 细胞中细胞表达谱的失调。我们还使用 siRNA 敲低（KD）了一些 U251 细胞蛋白，并观察它们对寨卡病毒复制和感染性的影响；
(3) 结果与结论：寨卡病毒失调的主要细胞网络是抗菌反应、细胞死亡和能量产生，而失调的主要功能是抗原呈递、病毒复制和细胞病变作用。Th1 和干扰素信号通路是失调的主要经典途径之一。siRNA 介导的 HLA-A、IGFBP5、PSMA2 和 HSPA5 的 KD 增加了寨卡病毒滴度和蛋白合成，表明它们是寨卡病毒限制因子。寨卡病毒感染也通过 48 小时后感染恢复了 HLA-A KD 细胞中的 HLA-A 表达，表明该基因产物与寨卡病毒之间存在相互作用。
