Immunology Catalyst, Immunology Network, GlaxoSmithKline, Gunnels Wood Road, Stevenage, Hertfordshire, SG1 2NY, UK.
Cardiff University, Institute of Infection and Immunity, School of Medicine, University Hospital of Wales, Heath Park, Cardiff, CF14, UK.
Nat Commun. 2022 Mar 17;13(1):1406. doi: 10.1038/s41467-022-28745-3.
Human rhinovirus (HRV), like coronavirus (HCoV), are positive-strand RNA viruses that cause both upper and lower respiratory tract illness, with their replication facilitated by concentrating RNA-synthesizing machinery in intracellular compartments made of modified host membranes, referred to as replication organelles (ROs). Here we report a non-canonical, essential function for stimulator of interferon genes (STING) during HRV infections. While the canonical function of STING is to detect cytosolic DNA and activate inflammatory responses, HRV infection triggers the release of STIM1-bound STING in the ER by lowering Ca, thereby allowing STING to interact with phosphatidylinositol 4-phosphate (PI4P) and traffic to ROs to facilitates viral replication and transmission via autophagy. Our results thus hint a critical function of STING in HRV viral replication and transmission, with possible implications for other RO-mediated RNA viruses.
人鼻病毒（HRV）与冠状病毒（HCoV）一样，属于正链 RNA 病毒，可引起上呼吸道和下呼吸道疾病，其复制过程依赖于将 RNA 合成机制集中在由宿主膜修饰而成的细胞内隔室（称为复制细胞器（RO））中。在此，我们报道了干扰素基因刺激物（STING）在 HRV 感染过程中的一个非经典的、必需的功能。虽然 STING 的典型功能是检测细胞质 DNA 并激活炎症反应，但 HRV 感染通过降低 Ca2+ 触发内质网中 STIM1 结合的 STING 的释放，从而允许 STING 与磷酸肌醇 4-磷酸（PI4P）相互作用并转运到 RO 中，促进病毒复制和通过自噬进行传播。因此，我们的研究结果提示 STING 在 HRV 病毒复制和传播中具有关键作用，这可能对其他 RO 介导的 RNA 病毒有一定影响。
