Wong Ho Him, Crudgington Dorian Richard Kenneth, Siu Lewis, Sanyal Sumana
HKU-Pasteur Research Pole, School of Public Health, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR.
Sir William Dunn School of Pathology, South Parks Road, University of Oxford, Oxford, United Kingdom.
PLoS Pathog. 2024 Dec 2;20(12):e1012766. doi: 10.1371/journal.ppat.1012766. eCollection 2024 Dec.
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.
黄病毒精心策划了内质网（ER）的独特重塑，以促进其多聚蛋白的翻译和加工，从而形成病毒复制区室。虽然信号识别颗粒（SRP）依赖途径是新生细胞膜蛋白靶向内质网的经典途径，但尚不清楚黄病毒是否依赖这一机制。在此，我们表明寨卡病毒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，与流感等其他病毒不同，寨卡病毒似乎通过NS3-SRP54相互作用维持内质网定位的翻译。病毒蛋白与SRP54和转运体结合，选择性地富集支持膜扩张和脂质代谢的因子，同时排除RNA结合蛋白和抗病毒应激颗粒蛋白。我们的研究结果揭示了一种复杂的病毒策略，即重新连接宿主蛋白合成途径并创建一个有利于复制的亚细胞生态位，为病毒适应性提供了见解。
