Savidis George, McDougall William M, Meraner Paul, Perreira Jill M, Portmann Jocelyn M, Trincucci Gaia, John Sinu P, Aker Aaron M, Renzette Nicholas, Robbins Douglas R, Guo Zhiru, Green Sharone, Kowalik Timothy F, Brass Abraham L
Department of Microbiology and Physiological Systems (MaPS), University of Massachusetts Medical, School, Worcester, MA 01655, USA.
Signaling Systems Unit, Laboratory of Systems Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Cell Rep. 2016 Jun 28;16(1):232-246. doi: 10.1016/j.celrep.2016.06.028. Epub 2016 Jun 21.
The flaviviruses dengue virus (DENV) and Zika virus (ZIKV) are severe health threats with rapidly expanding ranges. To identify the host cell dependencies of DENV and ZIKV, we completed orthologous functional genomic screens using RNAi and CRISPR/Cas9 approaches. The screens recovered the ZIKV entry factor AXL as well as multiple host factors involved in endocytosis (RAB5C and RABGEF), heparin sulfation (NDST1 and EXT1), and transmembrane protein processing and maturation, including the endoplasmic reticulum membrane complex (EMC). We find that both flaviviruses require the EMC for their early stages of infection. Together, these studies generate a high-confidence, systems-wide view of human-flavivirus interactions and provide insights into the role of the EMC in flavivirus replication.
黄病毒属的登革病毒（DENV）和寨卡病毒（ZIKV）对健康构成严重威胁，且传播范围正在迅速扩大。为了确定DENV和ZIKV对宿主细胞的依赖性，我们使用RNA干扰和CRISPR/Cas9方法完成了直系同源功能基因组筛选。筛选结果发现了ZIKV的进入因子AXL以及多个参与内吞作用（RAB5C和RABGEF）、硫酸乙酰肝素化作用（NDST1和EXT1）和跨膜蛋白加工与成熟（包括内质网膜复合物（EMC））的宿主因子。我们发现这两种黄病毒在感染早期都需要EMC。这些研究共同产生了关于人类与黄病毒相互作用的高可信度、全系统观点，并为EMC在黄病毒复制中的作用提供了见解。
