Papon Laura, Oteiza Alexandra, Imaizumi Tadaatsu, Kato Hiroki, Brocchi Emiliana, Lawson T Glen, Akira Shizuo, Mechti Nadir
Université Montpellier 1, Centre d'études d'agents Pathogènes et Biotechnologies pour la Santé (CPBS), F-34095 Montpellier, France.
Virology. 2009 Oct 25;393(2):311-8. doi: 10.1016/j.virol.2009.08.009. Epub 2009 Sep 4.
RNA helicase-like receptors MDA-5 but not RIG-I has been shown to be essential for triggering innate immune responses against picornaviruses. However, virus-host co-evolution has selected for viruses capable of replicating despite host cells antiviral defences. In this report, we demonstrate that RIG-I is degraded during encephalomyocarditis virus (EMCV) infection. This effect is mediated by both the viral-encoded 3C protease and caspase proteinase. In addition, we show that RIG-I overexpression confers IFN-beta promoter activation during EMCV infection, in MDA-5 knockout (MDA-5(-/-)) mouse embryo fibroblasts. This induction is followed by a strong inhibition reflecting the ability of EMCV to disrupt RIG-I signalling. Taken together, our data strongly suggest that during evolution RIG-I has been involved for triggering innate immune response to picornavirus infections.
已证明，RNA解旋酶样受体黑色素瘤分化相关基因5（MDA-5）而非视黄酸诱导基因I（RIG-I）对于触发针对小核糖核酸病毒的先天性免疫反应至关重要。然而，病毒与宿主的共同进化使得一些病毒即便在宿主细胞的抗病毒防御机制存在的情况下仍能进行复制。在本报告中，我们证明在脑心肌炎病毒（EMCV）感染期间RIG-I会被降解。这种效应是由病毒编码的3C蛋白酶和半胱天冬酶蛋白酶共同介导的。此外，我们还表明，在MDA-5基因敲除（MDA-5(-/-)）的小鼠胚胎成纤维细胞中，RIG-I的过表达会在EMCV感染期间赋予干扰素-β启动子激活能力。这种诱导随后会受到强烈抑制，这反映了EMCV破坏RIG-I信号传导的能力。综上所述，我们的数据有力地表明，在进化过程中，RIG-I参与了触发针对小核糖核酸病毒感染的先天性免疫反应。
