Xin Qi-Lin, Deng Cheng-Lin, Chen Xi, Wang Jun, Wang Shao-Bo, Wang Wei, Deng Fei, Zhang Bo, Xiao Gengfu, Zhang Lei-Ke
Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, China.
Wuhan Institute of Biotechnology, Wuhan, China.
J Virol. 2017 May 26;91(12). doi: 10.1128/JVI.00554-17. Print 2017 Jun 15.
Zika virus (ZIKV) is an emerging arbovirus belonging to the genus of the family During replication processes, flavivirus manipulates host cell systems to facilitate its replication, while the host cells activate antiviral responses. Identification of host proteins involved in the flavivirus replication process may lead to the discovery of antiviral targets. The mosquitoes and are epidemiologically important vectors for ZIKV, and effective restrictions of ZIKV replication in mosquitoes will be vital in controlling the spread of virus. In this study, an iTRAQ-based quantitative proteomic analysis of ZIKV-infected C6/36 cells was performed to investigate host proteins involved in the ZIKV infection process. A total of 3,544 host proteins were quantified, with 200 being differentially regulated, among which CHCHD2 can be upregulated by ZIKV infection in both mosquito C6/36 and human HeLa cells. Our further study indicated that CHCHD2 can promote ZIKV replication and inhibit beta interferon (IFN-β) production in HeLa cells, suggesting that ZIKV infection may upregulate CHCHD2 to inhibit IFN-I production and thus promote virus replication. Bioinformatics analysis of regulated host proteins highlighted several ZIKV infection-regulated biological processes. Further study indicated that the ubiquitin proteasome system (UPS) plays roles in the ZIKV entry process and that an FDA-approved inhibitor of the 20S proteasome, bortezomib, can inhibit ZIKV infection Our study illustrated how host cells respond to ZIKV infection and also provided a candidate drug for the control of ZIKV infection in mosquitoes and treatment of ZIKV infection in patients. ZIKV infection poses great threats to human health, and there is no FDA-approved drug available for the treatment of ZIKV infection. During replication, ZIKV manipulates host cell systems to facilitate its replication, while host cells activate antiviral responses. Identification of host proteins involved in the ZIKV replication process may lead to the discovery of antiviral targets. In this study, the first quantitative proteomic analysis of ZIKV-infected cells was performed to investigate host proteins involved in the ZIKV replication process. Bioinformatics analysis highlighted several ZIKV infection-regulated biological processes. Further study indicated that the ubiquitin proteasome system (UPS) plays roles in the ZIKV entry process and that an FDA-approved inhibitor of the UPS, bortezomib, can inhibit ZIKV infection Our study not only illustrated how host cells respond to ZIKV infection but also provided a candidate drug for the control of ZIKV infection in mosquitoes and treatment of ZIKV infection in patients.
寨卡病毒(ZIKV)是一种新出现的虫媒病毒,属于黄病毒科黄病毒属。在复制过程中,黄病毒会操纵宿主细胞系统以促进自身复制,而宿主细胞则会激活抗病毒反应。鉴定参与黄病毒复制过程的宿主蛋白可能会促成抗病毒靶点的发现。埃及伊蚊和白纹伊蚊是寨卡病毒在流行病学上的重要传播媒介,有效限制寨卡病毒在蚊子体内的复制对于控制病毒传播至关重要。在本研究中,我们对寨卡病毒感染的埃及伊蚊C6/36细胞进行了基于iTRAQ的定量蛋白质组学分析,以研究参与寨卡病毒感染过程的宿主蛋白。共鉴定出3544种宿主蛋白,其中200种存在差异调节,其中CHCHD2在蚊子C6/36细胞和人类HeLa细胞中均可被寨卡病毒感染上调。我们的进一步研究表明,CHCHD2可促进HeLa细胞中寨卡病毒的复制并抑制β干扰素(IFN-β)的产生,这表明寨卡病毒感染可能上调CHCHD2以抑制I型干扰素的产生,从而促进病毒复制。对受调节的宿主蛋白进行生物信息学分析突出了几个受寨卡病毒感染调节的生物学过程。进一步研究表明,泛素蛋白酶体系统(UPS)在寨卡病毒进入过程中发挥作用,一种FDA批准的20S蛋白酶体抑制剂硼替佐米可抑制寨卡病毒感染。我们的研究阐明了宿主细胞对寨卡病毒感染的反应方式,也为控制蚊子体内寨卡病毒感染和治疗患者寨卡病毒感染提供了一种候选药物。寨卡病毒感染对人类健康构成巨大威胁,目前尚无FDA批准的药物可用于治疗寨卡病毒感染。在复制过程中,寨卡病毒操纵宿主细胞系统以促进自身复制,而宿主细胞则激活抗病毒反应。鉴定参与寨卡病毒复制过程的宿主蛋白可能会促成抗病毒靶点的发现。在本研究中,我们首次对寨卡病毒感染的细胞进行了定量蛋白质组学分析,以研究参与寨卡病毒复制过程的宿主蛋白。生物信息学分析突出了几个受寨卡病毒感染调节的生物学过程。进一步研究表明,泛素蛋白酶体系统(UPS)在寨卡病毒进入过程中发挥作用,一种FDA批准的UPS抑制剂硼替佐米可抑制寨卡病毒感染。我们的研究不仅阐明了宿主细胞对寨卡病毒感染的反应方式,也为控制蚊子体内寨卡病毒感染和治疗患者寨卡病毒感染提供了一种候选药物。