Department of Microbiology and Immunology, Tulane University, New Orleans, Louisiana, USA.
Department of Craniofacial Biomedicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
J Med Virol. 2024 Nov;96(11):e70020. doi: 10.1002/jmv.70020.
Stimulator of interferon genes (STING) is an endoplasmic reticulum (ER) protein that plays a crucial role in cytosolic DNA-mediated innate immunity. Both STING agonists and antagonists have demonstrated their ability to enhance mouse survival against coronavirus, however, the physiological role of endogenous STING in coronavirus infection remains unclear. Our research unveils that STING inhibits coronavirus replication by impeding the formation of the ER-derived double-membrane vesicles (DMVs), the organelles in which coronavirus replicates. We found that STING was still capable of inhibiting coronavirus OC43 infection in cells, regardless of the knockout of cGAS or MAVS, or blocking type I interferon receptor. Moreover, STING disrupted the interaction between two crucial proteins, NSP4 and NSP6, involved in DMV formation, leading to the disruption of DMV formation. Taken together, our study sheds light on a novel antiviral role of STING in coronavirus infection, elucidating how it disrupts the formation of viral replication organelles, thereby impeding the replication process.
干扰素基因刺激蛋白（STING）是一种内质网（ER）蛋白，在细胞质 DNA 介导的先天免疫中发挥关键作用。STING 激动剂和拮抗剂都已证明能够提高小鼠对冠状病毒的存活率，然而，内源性 STING 在冠状病毒感染中的生理作用仍不清楚。我们的研究揭示，STING 通过阻碍冠状病毒复制所需的内质网衍生双层膜囊泡（DMVs）的形成来抑制冠状病毒复制。我们发现，STING 仍然能够抑制细胞中的冠状病毒 OC43 感染，无论 cGAS 或 MAVS 是否被敲除，或者阻断 I 型干扰素受体。此外，STING 破坏了参与 DMV 形成的两个关键蛋白 NSP4 和 NSP6 之间的相互作用，导致 DMV 形成中断。总之，我们的研究揭示了 STING 在冠状病毒感染中的一种新的抗病毒作用机制，阐明了它如何破坏病毒复制细胞器的形成，从而阻碍复制过程。
