Stimulator of interferon genes (STING) inhibits coronavirus infection by disrupting viral replication organelles

IF 6.8 3区 医学 Q1 VIROLOGY Journal of Medical Virology Pub Date : 2024-10-29 DOI:10.1002/jmv.70020
Kun Song, Abdul Hasan, Wenzhuo Hao, Yakun Wu, Yiwen Sun, Wenjun Li, Lingyan Wang, Shitao Li
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Abstract

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.

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干扰素基因刺激器(STING)通过破坏病毒复制细胞器来抑制冠状病毒感染。
干扰素基因刺激因子(STING)是一种内质网(ER)蛋白,在细胞膜 DNA 介导的先天性免疫中起着至关重要的作用。STING 激动剂和拮抗剂都能提高小鼠对冠状病毒的存活率,但内源性 STING 在冠状病毒感染中的生理作用仍不清楚。我们的研究揭示了 STING 可通过阻碍 ER 衍生的双膜囊泡(DMVs)的形成来抑制冠状病毒的复制,而 ER 衍生的双膜囊泡正是冠状病毒复制的细胞器。我们发现,无论敲除cGAS或MAVS,还是阻断I型干扰素受体,STING仍能抑制冠状病毒OC43在细胞中的感染。此外,STING还破坏了参与DMV形成的两个关键蛋白NSP4和NSP6之间的相互作用,导致DMV的形成被破坏。综上所述,我们的研究揭示了 STING 在冠状病毒感染中的新型抗病毒作用,阐明了 STING 如何破坏病毒复制细胞器的形成,从而阻碍病毒的复制过程。
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来源期刊
Journal of Medical Virology
Journal of Medical Virology 医学-病毒学
CiteScore
23.20
自引率
2.40%
发文量
777
审稿时长
1 months
期刊介绍: The Journal of Medical Virology focuses on publishing original scientific papers on both basic and applied research related to viruses that affect humans. The journal publishes reports covering a wide range of topics, including the characterization, diagnosis, epidemiology, immunology, and pathogenesis of human virus infections. It also includes studies on virus morphology, genetics, replication, and interactions with host cells. The intended readership of the journal includes virologists, microbiologists, immunologists, infectious disease specialists, diagnostic laboratory technologists, epidemiologists, hematologists, and cell biologists. The Journal of Medical Virology is indexed and abstracted in various databases, including Abstracts in Anthropology (Sage), CABI, AgBiotech News & Information, National Agricultural Library, Biological Abstracts, Embase, Global Health, Web of Science, Veterinary Bulletin, and others.
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