通过NF-κB和干扰素通路,CSF3增强了对ALV-J感染的先天免疫反应
Junliang Xia1, Weiding Chen1, Chengxun Xu1
1Department of Animal Genetics, Breeding and Reproduction, College of Animal Science, South China Agricultural University, Guangzhou, Guangdong, China; Guangdong Provincial Key Laboratory of Agro-Animal Genomics and Molecular Breeding, and Key Lab of Chicken Genetics, Breeding and Reproduction, Ministry of Agriculture and Rural Affair, Guangzhou, Guangdong, China; State Key Laboratory of Swine and Poultry Breeding Industry, Guangzhou, China.
颗粒细胞殖民地刺激因子3 (CSF3) 增强了对禽类白血病病毒 (ALV) 的禽类免疫反应. CSF3激活抗病毒通路,为禽类提供抗病和预防策略的潜力.
科学领域:
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
- 分子生物学分子生物学
背景情况:
- 禽类白血病病毒 (ALVs) 由于免疫抑制和瘤发生,导致家禽的经济损失很大.
- 目前针对ALV的疫苗和抗病毒药物有限,需要新的控制策略.
- 颗粒细胞殖民地刺激因子3 (CSF3) 是一种参与免疫细胞调节的细胞因子,其在ALV感染中的作用以前未被描述.
研究的目的:
- 研究CSF3在宿主对禽类白血病病毒 (ALV) 的天生的免疫反应中的作用.
- 阐明通过CSF3影响ALV感染的分子机制.
- 探索CSF3作为ALV控制的治疗或育种点的潜力.
主要方法:
- 分析了CSF3促进剂活性,使用ALV和多诺西尼克-多乙烯酸 (多I:C) 刺激的记者结构.
- 在DF-1细胞和初级纤维细胞中,CSF3过度表达和沉默,随后发生ALV-J感染.
- 转录组分析,蛋白质酸化的西方抹杀和抑制剂研究 (STAT3抑制剂) 用于评估信号通路.
主要成果:
- ALV和多I:C激活了CSF3促进体,而玛激活序列 (GAS) 可能作为反应元素.
- 通过TLR,RIG-I,JAK/STAT和NF-κB通路,CSF3过度表达升高了抗病毒和炎症基因 (例如IRF7,Mx,MDA5) 的调节.
- CSF3增强了STAT3酸化,促进了促炎性细胞因子的产生,激活了NF-κB,并抑制了ALV-J包膜糖蛋白的表达.
结论:
- CSF3作为一种非典型的干扰素刺激基因 (ISG) 起作用,增强了对ALV-J的先天免疫防御能力.
- CSF3的抗病毒活性通过激活NF-κB和干扰素依赖的抗病毒机制来调节,涉及STAT3酸化.
- CSF3具有作为家禽养殖候选耐药性基因或作为ALV预防疫苗辅助剂的潜力.
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