远鱼TRPV4与DEAD盒RNA酶1的相互作用 调节疹病毒复制
Zhiyong Luo1,2,3,4, Zhipeng Zhan1,2,3,4, Xiaowei Qin1,2,3,4
1State Key Laboratory for Biocontrol, School of Marine Sciences, Sun Yat-sen University, Guangzhou, People's Republic of China.
Journal of virology
|June 8, 2023
概括
瞬态受体潜在化物4 (TRPV4) 通道和DEAD盒RNA酶1 (DDX1) 轴通过调解流入和与病毒RNA相互作用,促进鱼类中的病毒复制. 这一发现为预防水产养殖病毒病提供了新的策略.
科学领域:
- 分子生物学分子生物学
- 水产养殖病理学 水产养殖病理学
- 病毒学 病毒学
背景情况:
- 病毒性疾病对全球水产养殖行业构成重大威胁,造成了巨大的经济损失.
- 暂时受体潜在化物4 (TRPV4) 在调节病毒活性中的作用在哺乳动物中已知,但在远鱼中未被表征.
- 了解宿主病毒相互作用对于开发水产养殖中有效的疾病控制策略至关重要.
研究的目的:
- 研究TRPV4-DEAD盒RNA酶1 (DDX1)轴在鱼 (Siniperca chuatsi) 中病毒感染中的作用.
- 阐明TRPV4和DDX1影响病毒复制的分子机制.
- 探索这个轴在调节包括哺乳动物在内的不同物种病毒感染方面的潜力.
主要方法:
- 研究了TRPV4激活和透性突变体 (M709D) 对感染性脏亡病毒 (ISKNV) 复制的影响.
- 在ISKNV感染期间测量细胞内 (Ca2+) 度.
- 通过域映射 (TRPV4的N端域和DDX1的C端域) 分析了TRPV4和DDX1之间的相互作用.
- 评估了DDX1的ATPase/helicase活性在结合病毒mRNA和促进ISKNV复制中的作用.
- 验证了TRPV4-DDX1轴在调节哺乳动物细胞中简单疹病毒1复制中的作用.
主要成果:
- TRPV4激活通过调解Ca2+流入来增强ISKNV复制,这一过程被M709D突变显著减少.
- 感染ISKNV会增加细胞Ca2+水平,这对病毒复制至关重要.
- TRPV4与DDX1相互作用,通过TRPV4激活来减弱相互作用,从而促进ISKNV复制.
- DDX1与病毒mRNA结合,并需要其ATPase/helicase活性来促进ISKNV复制.
- 证实TRPV4-DDX1轴能够调节在哺乳动物细胞中的简单疹病毒1复制.
结论:
- TRPV4-DDX1轴在促进远鱼的病毒复制中发挥着关键作用,为宿主抗病毒调节提供了一种新的分子机制.
- 通过Ca2+流入,TRPV4通过调节其与DDX1的相互作用来促进病毒复制,DDX1与病毒RNA结合.
- 这项研究提供了对宿主病毒相互作用的基本见解,可能有助于开发新的预防和控制水产养殖病毒病的战略.
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