Institute of Pathogen Biology and Immunology, College of Biology, Hunan Provincial Key Laboratory of Medical Virology, Hunan University, Changsha 410082, Hunan, China.
State Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, Hubei, China.
Virus Res. 2020 Sep;286:198074. doi: 10.1016/j.virusres.2020.198074. Epub 2020 Jun 23.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel human coronavirus causing the pandemic of severe pneumonia (Coronavirus Disease 2019, COVID-19). SARS-CoV-2 is highly pathogenic in human, having posed immeasurable public health challenges to the world. Innate immune response is critical for the host defense against viral infection and the dysregulation of the host innate immune responses probably aggravates SARS-CoV-2 infection, contributing to the high morbidity and lethality of COVID-19. It has been reported that some coronavirus proteins play an important role in modulating innate immunity of the host, but few studies have been conducted on SARS-CoV-2. In this study, we screened the viral proteins of SARS-CoV-2 and found that the viral ORF6, ORF8 and nucleocapsid proteins were potential inhibitors of type I interferon signaling pathway, a key component for antiviral response of host innate immune. All the three proteins showed strong inhibition on type I interferon (IFN-β) and NF-κB-responsive promoter, further examination revealed that these proteins were able to inhibit the interferon-stimulated response element (ISRE) after infection with Sendai virus, while only ORF6 and ORF8 proteins were able to inhibit the ISRE after treatment with interferon beta. These findings would be helpful for the further study of the detailed signaling pathway and unveil the key molecular player that may be targeted.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）是一种新型人类冠状病毒，可引发严重肺炎大流行（2019 年冠状病毒病，COVID-19）。SARS-CoV-2 在人类中具有高度致病性，对世界造成了不可估量的公共卫生挑战。先天免疫反应对于宿主抵抗病毒感染至关重要，而宿主先天免疫反应的失调可能会加重 SARS-CoV-2 感染，导致 COVID-19 的高发病率和死亡率。据报道，一些冠状病毒蛋白在调节宿主先天免疫方面发挥着重要作用，但针对 SARS-CoV-2 的研究较少。在这项研究中，我们筛选了 SARS-CoV-2 的病毒蛋白，发现病毒 ORF6、ORF8 和核衣壳蛋白可能是宿主先天免疫抗病毒反应的关键组成部分之一——I 型干扰素信号通路的抑制剂。这三种蛋白均对 I 型干扰素（IFN-β）和 NF-κB 反应启动子表现出强烈的抑制作用，进一步的研究表明，这些蛋白在感染仙台病毒后能够抑制干扰素刺激反应元件（ISRE），而只有 ORF6 和 ORF8 蛋白在使用干扰素β处理后能够抑制 ISRE。这些发现有助于进一步研究详细的信号通路，并揭示可能成为靶向目标的关键分子。
