ASFV pA151R通过降解E3结合酶TRAF6负面调节I型IFN的产生
You Li1,2,3,4, Li Huang5, Hui Li1,2,3,4
1State Key Laboratory of Animal Biotech Breeding, China Agricultural University, Beijing, China.
Frontiers in immunology
|March 7, 2024
概括
非洲猪瘟病毒 (ASFV) 蛋白质pA151R通过降解TRAF6抑制I型干扰素的产生,从而阻碍抗病毒免疫力. 抑制pA151R可以抑制ASFV的复制,并增加猪的干扰素产量.
科学领域:
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
- 分子生物学分子生物学
背景情况:
- 非洲猪瘟 (ASF) 是一种严重的猪病,由非洲猪瘟病毒 (ASFV) 引起.
- 众所周知,ASFV会干扰宿主干扰素 (IFN) 生产,这是一个关键的抗病毒防御机制.
研究的目的:
- 研究ASFV蛋白pA151R在调节I型IFN产生的作用.
- 阐明pA151R影响cGAS-STING信号通路和宿主抗病毒反应的分子机制.
主要方法:
- 细胞中ASFV pA151R的宫外表达.
- 分析TBK1的泛化和酸化.
- 同免疫沉以研究蛋白质相互作用.
- 西方涂抹检测蛋白质降解.
- 病毒复制试验 (ASFV和HSV-1).
- 在猪膜巨细胞 (PAMs) 中,siRNA介导的pA151R的淘汰.
主要成果:
- 发现ASFV pA151R可以负面调节I型IFN的产生.
- pA151R 抑制了 TBK1.1 的 K63 相关的多比基因化和 Ser172 酸化.
- pA151R与E3酶TRAF6相互作用并促进其降解,破坏了TBK1-TRAF6的相互作用.
- 在pA151R中的特定氨基酸 (H102,C109,C132,C135) 对其抑制功能至关重要.
- 过度表达pA151R增强了简单疹病毒1 (HSV-1) 复制,通过抑制IFN-β的产生.
- 抑制pA151R降低了ASFV复制和增加了PAM中的IFN-β产量.
结论:
- ASFV pA151R 是一种类型I IFN 生产的病毒抗剂,通过降解TRAF6和随后的TBK1激活中断而起作用.
- 这种机制使ASFV能够逃避宿主抗病毒免疫力.
- 针对pA151R可能是开发新型ASFV疫苗和治疗方法的策略.
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