寨卡病毒（ZIKV）感染孕妇能引起新生儿脑部畸形。通过CRISPR高通量筛选，我们发现线粒体融合蛋白MFN2是参与ZIKV复制的关键宿主因子。MFN2除了定位于线粒体中，也存在于内质网中。内质网上的MFN2参与线粒体-内质网接触的形成。我们也观察到ZIKV感染（MR766和ZG01毒株）的细胞中MFN2显著下调，而登革热病毒感染则没有。基于线粒体-内质网接触报告系统，初步研究结果表明ZIKV感染影响线粒体-内质网接触。究竟是线粒体还是内质网中的MFN2参与了ZIKV的复制？ZIKV是否通过降解MFN2，影响线粒体-内质网接触和信息交流？本项目将通过基因敲除、回补定位于线粒体或内质网的MFN2突变体、线粒体-内质网接触报告系统等，揭示MFN2参与ZIKV复制的分子机制，阐明ZIKV降解MFN2是否影响引起线粒体-内质网接触和信息交流，为揭示ZIKV的致病机制提供新的科学依据。

Zika virus (ZIKV) infection causes neurological disorder of newborns in pregnancy, such as microcephaly. We identified mitofusin 2 (MFN2) as a host factor of ZIKV by genome-wide CRISPR screening. MFN2, an outer mitochondrial membrane GTPase, is critical for mitochondrial fusion. Besides, MFN2 is also localized on the endoplasmic reticulum (ER), where MFN2 tethers ER to mitochondria through interacting with MFN1 or MFN2 on the mitochondria. We also found that MFN2 was significantly down-regulated in ZIKV (both MR766 and ZG01 strain), but not in Dengue virus infected cells. Our preliminary data showed that mitochondria-ER contact was disrupted based on a reporter of mitochondria-ER contacts in ZIKV infected cells. We wonder whether MFN2 on the mitochondria or ER plays a role in ZIKV replication, and whether the degradation of MFN2 disrupts mitochondria-ER contacts in ZIKV infected cells. Therefore, we will investigate the roles of MFN2 in ZIKV life cycle, and figure out whether ZIKV caused degradation of MFN2 damages mitochondria-ER contracts and communication.