List of DsiRNA used in this study.

Flaviviruses orchestrate a unique remodelling of the endoplasmic reticulum (ER) to facilitate translation and processing of their polyprotein, giving rise to virus replication compartments. While the signal recognition particle (SRP)-dependent pathway is the canonical route for ER-targeting of nascent cellular membrane proteins, it is unknown whether flaviviruses rely on this mechanism. Here we show that Zika virus bypasses the SRP receptor via extensive interactions between the viral non-structural proteins and the host translational machinery. Remarkably, Zika virus appears to maintain ER-localised translation via NS3-SRP54 interaction instead, unlike other viruses such as influenza. Viral proteins engage SRP54 and the translocon, selectively enriching for factors supporting membrane expansion and lipid metabolism while excluding RNA binding and antiviral stress granule proteins. Our findings reveal a sophisticated viral strategy to rewire host protein synthesis pathways and create a replication-favourable subcellular niche, providing insights into viral adaptation.

黄病毒（Flaviviruses）会对宿主内质网（endoplasmic reticulum, ER）进行独特的重塑，以促进自身多聚蛋白的翻译与加工，进而形成病毒复制区室。信号识别颗粒（signal recognition particle, SRP）依赖途径是新生宿主细胞膜蛋白靶向内质网的经典途径，但目前尚不清楚黄病毒是否依赖这一机制。本研究显示，寨卡病毒（Zika virus）通过病毒非结构蛋白与宿主翻译机器之间的广泛相互作用，绕过了SRP受体。值得注意的是，与流感病毒等其他病毒不同，寨卡病毒似乎通过NS3与SRP54的相互作用来维持内质网定位的翻译过程。病毒蛋白与SRP54及易位复合体（translocon）结合，选择性富集支持膜扩张与脂质代谢的宿主因子，同时排除RNA结合蛋白与抗病毒应激颗粒蛋白。本研究揭示了一种精妙的病毒策略，可重塑宿主蛋白质合成通路并构建利于病毒复制的亚细胞微环境，为病毒适应机制的研究提供了新的见解。