She Gaoli, Zhong Chunhui, Pan Yue, Chen Zexin, Li Jingmin, Li Mingchong, Liu Yufang, Cao Yongchang, Wei Xiaona, Xue Chunyi
State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou 510275, China.
School of Life Sciences, Zhengzhou University, Zhengzhou 450001, China.
Microorganisms. 2025 Jun 26;13(7):1494. doi: 10.3390/microorganisms13071494.
Swine acute diarrhea syndrome coronavirus (SADS-CoV), initially identified in China in February 2017, severely impacts the swine industry by causing lethal watery diarrhea in neonatal piglets. Understanding the molecular mechanism employed by SADS-CoV to evade the host's immune defenses is of utmost importance. In this study, using the porcine ileum epithelial cell line IPI-FX as an in vitro model, we investigated the highly pathogenic SADS-CoV GDS04 strain and its nonstructural protein 5 (nsp5) for their roles in inhibiting interferon-beta (IFN-β) production. Our findings indicated that GDS04 inhibited poly(I:C)-induced IFN-β production by impeding the promoter activities of IRF3 and NF-κB. As a 3C-like protease, SADS-CoV nsp5 functioned as an interferon inhibitor by interacting with IKKε, reducing its protein abundance, and inhibiting its phosphorylation. This study enhances our understanding of the interaction between coronaviruses and their hosts, providing novel insights into the evasion of the immune system by coronaviruses.
猪急性腹泻综合征冠状病毒（SADS-CoV）于2017年2月首次在中国被发现，它通过引起新生仔猪致命性水样腹泻，对养猪业造成严重影响。了解SADS-CoV用于逃避宿主免疫防御的分子机制至关重要。在本研究中，我们以猪回肠上皮细胞系IPI-FX作为体外模型，研究了高致病性SADS-CoV GDS04毒株及其非结构蛋白5（nsp5）在抑制干扰素-β（IFN-β）产生中的作用。我们的研究结果表明，GDS04通过阻碍IRF3和NF-κB的启动子活性来抑制聚肌苷酸-聚胞苷酸（poly(I:C)）诱导的IFN-β产生。作为一种类3C蛋白酶，SADS-CoV nsp5通过与IKKε相互作用、降低其蛋白丰度并抑制其磷酸化，发挥干扰素抑制剂的作用。本研究增进了我们对冠状病毒与其宿主之间相互作用的理解，为冠状病毒逃避免疫系统提供了新的见解。
