OBJECTIVES The molecular mechanisms underlying the pathogenesis of human coronavirus OC43 (HCoV-OC43) infection are poorly understood. In this study, we investigated the ability of HCoV-OC43 to antagonize the transcriptional activation of antiviral response elements. METHODS HCoV-OC43 structural (membrane M and nucleocapsid N) and accessory proteins (ns2a and ns5a) were expressed individually in human embryonic kidney 293 (HEK-293) cells. The transcriptional activation of antiviral response elements was assessed by measuring the levels of firefly luciferase expressed under the control of interferon (IFN)-stimulated response element (ISRE), IFN-β promoter, or nuclear factor kappa B response element (NF-κB-RE). The antiviral gene expression profile in HEK-293 cells was determined by PCR array. RESULTS The transcriptional activity of ISRE, IFN-β promoter, and NF-κB-RE was significantly reduced in the presence of HCoV-OC43 ns2a, ns5a, M, or N protein, following the challenge of cells with Sendai virus, IFN-α or tumor necrosis factor-α. The expression of antiviral genes involved in the type I IFN and NF-κB signaling pathways was also downregulated in the presence of HCoV-OC43 structural or accessory proteins. CONCLUSION Both structural and accessory HCoV-OC43 proteins are able to inhibit antiviral response elements in HEK-293 cells, and to block the activation of different antiviral signaling pathways.

中文翻译：

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人类冠状病毒OC43结构蛋白和附件蛋白对抗病毒应答元件转录激活的影响。

目的人们对人类冠状病毒OC43（HCoV-OC43）感染发病机理的分子机制了解甚少。在这项研究中，我们调查了HCoV-OC43拮抗抗病毒应答元件转录激活的能力。方法HCoV-OC43的结构（膜M和核衣壳N）和辅助蛋白（ns2a和ns5a）分别在人胚胎肾293（HEK-293）细胞中表达。通过测量在干扰素（IFN）刺激的反应元件（ISRE），IFN-β启动子或核因子κB反应元件（NF-κB-）的控制下表达的萤火虫荧光素酶的水平来评估抗病毒反应元件的转录激活。回覆）。通过PCR阵列确定HEK-293细胞中的抗病毒基因表达谱。结果ISRE的转录活性 在HCoV-OC43 ns2a，ns5a，M或N蛋白存在下，用仙台病毒，IFN-α或肿瘤坏死因子-α攻击细胞后，IFN-β启动子和NF-κB-RE显着降低。在HCoV-OC43结构蛋白或辅助蛋白的存在下，参与I型IFN和NF-κB信号通路的抗病毒基因的表达也被下调。结论HCoV-OC43结构蛋白和辅助蛋白均能够抑制HEK-293细胞中的抗病毒应答元件，并阻断不同抗病毒信号通路的激活。在HCoV-OC43结构蛋白或辅助蛋白的存在下，参与I型IFN和NF-κB信号通路的抗病毒基因的表达也被下调。结论HCoV-OC43结构蛋白和辅助蛋白均能够抑制HEK-293细胞中的抗病毒应答元件，并阻断不同抗病毒信号通路的激活。在HCoV-OC43结构蛋白或辅助蛋白的存在下，参与I型IFN和NF-κB信号通路的抗病毒基因的表达也被下调。结论HCoV-OC43结构蛋白和辅助蛋白均能够抑制HEK-293细胞中的抗病毒应答元件，并阻断不同抗病毒信号通路的激活。