SARS-CoV-2 Accessory Protein ORF7b Mediates Tumor Necrosis Factor-α-Induced Apoptosis in Cells.
SARS-CoV-2 Accessory Protein ORF7b Mediates Tumor Necrosis Factor-α-Induced Apoptosis in Cells.
复制标题
SARS-CoV-2 辅助蛋白 ORF7b 介导肿瘤坏死因子-α 诱导的细胞凋亡
DOI：
10.3389/fmicb.2021.654709
复制
发表时间：
2021
影响因子：
5.2
通讯作者：
Liu Z
中科院分区：
文献类型：
--
作者：
Yang R;Zhao Q;Rao J;Zeng F;Yuan S;Ji M;Sun X;Li J;Yang J;Cui J;Jin Z;Liu L;Liu Z
冠状病毒的辅助蛋白对于病毒-宿主相互作用和宿主免疫应答的调节是必需的。严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）编码的辅助蛋白ORF 3a具有诱导细胞凋亡的作用，辅助蛋白ORF 6和ORF 8可能是I型干扰素（IFN）信号通路的抑制剂。然而，辅助蛋白ORF 7 b的功能在很大程度上是未知的。我们研究了ORF 7 b在细胞中的凋亡诱导活性。同时检测了细胞因子水平和宿主天然免疫应答，包括干扰素调节转录因子（IRF）-3、信号转导和转录激活因子（STAT）-1、干扰素（IFN）-β、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的表达。我们发现ORF 7 b促进IFN-β、TNF-α和IL-6的表达，通过IRF 3磷酸化激活I型IFN信号，并激活TNFα诱导的HEK 293 T细胞和Vero E6细胞凋亡。这些结果为深入了解SARS-CoV-2的致病性以及辅助蛋白ORF 7 b与宿主免疫应答的相互作用提供了理论依据。
The accessory proteins of coronaviruses are essential for virus–host interactions and the modulation of host immune responses. It has been reported that accessory protein ORF3a encoded by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce apoptosis, and accessory protein ORF6 and ORF8 could be inhibitors of the type-I interferon (IFN) signaling pathway. However, the function of accessory protein ORF7b is largely unknown. We investigated the apoptosis-inducing activity of ORF7b in cells. Cytokine levels and host innate immune responses, including expression of interferon regulatory transcription factor (IRF)-3, signal transducer and activator of transcription (STAT)-1, interferon (IFN)-β, tumor necrosis factor (TNF)-α, and interleukin (IL)-6, were also investigated. We found that ORF7b promoted expression of IFN-β, TNF-α, and IL-6, activated type-I IFN signaling through IRF3 phosphorylation, and activated TNFα-induced apoptosis in HEK293T cells and Vero E6 cells. These results could provide deeper understanding about the pathogenicity of SARS-CoV-2 as well as the interaction between the accessory protein ORF7b with host immune responses.