Negative Regulation of MAVS-Mediated Innate Immune Response by PSMA7
Negative Regulation of MAVS-Mediated Innate Immune Response by PSMA7
复制标题
PSMA7 对 MAVS 介导的先天免疫反应的负调节
DOI：
10.4049/jimmunol.0901646
复制
发表时间：
2009-10-01
影响因子：
4.4
通讯作者：
Zhong, Hui
中科院分区：
文献类型：
--
作者：
Jia, Yongxia;Song, Ting;Zhong, Hui
对病毒的先天免疫涉及受体如视黄酸诱导基因-1（RIG-I），其感测病毒RNA并触发涉及线粒体外膜蛋白线粒体抗病毒信号传导（MAVS）的信号传导途径。最近的工作已经确定，NLRX 1，另一类先天免疫受体的成员，隔离MAVS远离RIG-I，从而防止线粒体抗病毒免疫。在这项研究中，我们证明了蛋白酶体PSMA 7（α 4）亚基与MAVS在体内和体外。PSMA 7的表达导致RIG-1和MAVS介导的IFN-β启动子活性的有效抑制;相反，用小干扰RNA耗尽PSMA 7增强病毒诱导的I型IFN产生，从而减少病毒复制。此外，发现具有过表达的PSMA 7的内源MAVS的丰度显著降低，并且病毒感染导致内源PSMA 7蛋白水平的瞬时增加。累积地，这些结果表明，PSMA 7是MAVS介导的先天免疫的负调节剂，其可能用于减弱病毒感染期间抗病毒状态的建立，突出了PSMA 7-MAVS关联作为重要的细胞调节控制的生物学意义。免疫学杂志，2009，183：4241-4248.
Innate immunity to viruses involves receptors such as Retinoic Acid Induced Gene-1 (RIG-I), which senses viral, RNA and triggers a signaling pathway involving the outer mitochondrial membrane protein mitochondrial antiviral signaling (MAVS). Recent work has identified that NLRX1, a member of another class of innate immune receptors, sequesters MAVS away from RIG-I and thereby prevents mitochondrial antiviral immunity. In this study, we demonstrate that the proteasome PSMA7 (alpha 4) subunit associates with MAVS in vivo and in vitro. Expression of PSMA7 results in a potent inhibition of RIG-1 and MAVS-mediated IFN-beta promoter activity; conversely, depletion of PSMA7 with small interference RNA enhances virus-induced type I IFN production, with consequent reduction of virus replication. Furthermore, a striking reduction in the abundance of endogenous MAVS with overexpressed PSMA7 was found and virus infection leads to transient increase in the endogenous PSMA7 protein level. Cumulatively, these results suggest that PSMA7 is a negative regulator of the MAVS-mediated innate immunity that probably serves to attenuate the establishment of an antiviral state during viral infection, highlighting the biological significance of PSMA7-MAVS association as an important cellular regulatory control. The Journal of Immunology, 2009, 183: 4241-4248.