Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, China.
Institute of Marine Sciences, Shantou University, Shantou, China.
PLoS Pathog. 2020 May 20;16(5):e1008366. doi: 10.1371/journal.ppat.1008366. eCollection 2020 May.
MicroRNAs are regulatory molecules that can be packaged into exosomes to modulate cellular response of recipients. While the role of exosomes during viral infection is beginning to be appreciated, the involvement of exosomal miRNAs in immunoregulation in invertebrates has not been addressed. Here, we observed that exosomes released from WSSV-injected mud crabs could suppress viral replication by inducing apoptosis of hemocytes. Besides, miR-137 and miR-7847 were found to be less packaged in mud crab exosomes during viral infection, with both miR-137 and miR-7847 shown to negatively regulate apoptosis by targeting the apoptosis-inducing factor (AIF). Our data also revealed that AIF translocated to the nucleus to induce DNA fragmentation, and could competitively bind to HSP70 to disintegrate the HSP70-Bax (Bcl-2-associated X protein) complex, thereby activating the mitochondria apoptosis pathway by freeing Bax. The present finding therefore provides a novel mechanism that underlies the crosstalk between exosomal miRNAs and apoptosis pathway in innate immune response in invertebrates.
微小 RNA 是一种调节分子，可以被包装到外泌体中，从而调节受体细胞的反应。虽然外泌体在病毒感染过程中的作用开始被人们所认识，但外泌体中的微小 RNA 在无脊椎动物的免疫调节中的参与尚未得到解决。在这里，我们观察到，从注射 WSSV 的泥蟹中释放的外泌体可以通过诱导血细胞凋亡来抑制病毒复制。此外，在病毒感染期间，miR-137 和 miR-7847 在外泌体中的包装量较少，miR-137 和 miR-7847 均通过靶向凋亡诱导因子（AIF）负调控凋亡。我们的数据还表明，AIF 易位到细胞核中诱导 DNA 片段化，并可以与 HSP70 竞争结合，破坏 HSP70-Bax（Bcl-2 相关 X 蛋白）复合物，从而通过释放 Bax 激活线粒体凋亡途径。因此，本研究结果提供了一种新的机制，阐明了无脊椎动物固有免疫反应中外泌体微小 RNA 和凋亡途径之间的串扰。
