除了JNK/P38通路之外,MAP3K15还通过背部CC-CL-STAT轴在甲类动物中促进多个病毒基因的表达
Xiao-Qin Ran1, Chen-Chen Liu1, Xue-Mei Xu1
1Shandong Provincial Key Laboratory of Animal Cells and Developmental Biology, School of Life Sciences, Shandong University, Qingdao, Shandong, China.
PLoS pathogens
|August 1, 2025
概括
MAP3K15 (亡信号调节激酶3,ASK3) 在白斑综合征病毒 (WSSV) 感染期间激活,促进病毒基因表达. 抑制MAP3K15有效控制了甲类动物中的WSSV.
科学领域:
- 分子生物学分子生物学
- 病毒学 病毒学
- 免疫学 免疫学 免疫学
背景情况:
- 线素激活蛋白激酶 (MAPK) 途径对于细胞对外部信号的反应至关重要.
- 虽然各种MAPK激酶激酶 (MAP3Ks) 参与了病原体的反应,但MAP3K15 (亡信号调节激酶3,ASK3) 在病毒感染中的作用仍然在很大程度上未被探索.
研究的目的:
- 在甲类动物感染DNA病毒 (白斑综合征病毒,WSSV) 期间调查MAP3K15的功能和机制.
- 探索针对MAP3K15在水产养殖中控制WSSV的潜在治疗策略.
主要方法:
- 在WSSV感染期间对MAP3K15进行酸化和激活试验.
- 同免疫沉研究MAP3K15和Dorsal (NF-κB同源) 之间的相互作用.
- 对基因表达 (CC-CL,病毒直接早期基因) 和信号通路激活 (JAK/STAT,JNK/P38) 的分析.
- 使用MAP3K15淘汰和特定抑制剂 (SDK1) 进行抑制研究,以评估病毒载量和宿主存活率.
主要成果:
- MAP3K15在WSSV感染时被酸化和激活.
- 激活的MAP3K15与Dorsal相互作用,促进其核转位和随后的CC-CL和病毒直接早期基因的表达.
- CC-CL激活了JAK/STAT通路,进一步提高了病毒基因表达的调节. JNK/P38通路的激活也会导致病毒基因表达.
- 抑制MAP3K15或抑制其活性形式可显著降低病毒放大,并改善各种甲类的宿主存活率.
结论:
- 通过调节宿主信号通路,MAP3K15在促进DNA病毒 (WSSV) 感染方面发挥着关键和保守的作用.
- 这项研究阐明了一种涉及MAP3K15,背部,CC-CL和JAK/STAT信号在WSSV病变发生过程中的新机制.
- 向MAP3K15为管理类水产养殖中的WSSV爆发提供了一个有希望的战略.
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