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PDCoV的非结构性蛋白14通过激活p38-MAPK-C/EBP通路促进补充C3的表达
Zhuoqi Chen1, Chunyan Zhong2, Liyuan Fan1
1Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology Ministry of Agriculture, Nanjing 210014, China; Jiangsu Key Laboratory for Food Quality and Safety-State Key Laboratory Cultivation Base of Ministry of Science and Technology, Nanjing 210014, China.
猪三角冠状病毒 (PDCoV) 激活补充成分3 (C3),抑制病毒复制. 特定的病毒蛋白质,特别是NSP14,可提高C3的表达,提供潜在的抗病毒点.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 猪健康 猪健康
背景情况:
- 猪三角冠状病毒 (PDCoV) 在猪中引起显著的肠道疾病,不完全理解病原机制.
- 补充成分3 (C3) 对于抗病毒防御至关重要,但其在PDCoV感染中的作用尚不清楚.
研究的目的:
- 调查PDCoV和补充成分3 (C3) 之间的相互作用.
- 阐明C3在PDCoV复制中的作用,并确定影响C3表达的病毒因素.
主要方法:
- 在细胞培养模型中的PDCoV感染.
- 对C3激活和表达水平的分析.
- 对C3.3的过度表达和抑制研究.
- 确定参与C3调节的PDCoV非结构蛋白 (Nsp7,Nsp14,M).
- 途径分析 (p38-MAPK-C/EBP-β) 和NSP14的局部导向突变发生.
主要成果:
- PDCoV激活C3并诱导炎症反应.
- 过度表达C3抑制了PDCoV复制;C3抑制增强了它.
- PDCoV非结构蛋白Nsp7,Nsp14和M刺激了C3的表达,Nsp14通过p38-MAPK-C/EBP-β通路特别有效.
- Nsp14的N7-MTase域,特别是D44和T135氨基酸,对于上调C3.3的调节至关重要.
结论:
- 通过抑制病毒复制,C3对PDCoV感染起着保护作用.
- PDCoV通过其非结构性蛋白质,特别是Nsp14来操纵宿主C3的表达,以促进感染.
- Nsp14-C3相互作用为开发针对PDCoV.病毒的抗病毒策略提供了潜在的目标.
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