Seth Rashu B, Sun Lijun, Chen Zhijian J
Howard Hughes Medical Institute, Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390-9148, USA.
Cell Res. 2006 Feb;16(2):141-7. doi: 10.1038/sj.cr.7310019.
Recent studies have uncovered two signaling pathways that activate the host innate immunity against viral infection. One of the pathways utilizes members of the Toll-like receptor (TLR) family to detect viruses that enter the endosome through endocytosis. The TLR pathway induces interferon production through several signaling proteins that ultimately lead to the activation of the transcription factors NF-kappaB, IRF3 and IRF7. The other antiviral pathway uses the RNA helicase RIG-I as the receptor for intracellular viral double-stranded RNA. RIG-I activates NF-kappaB and IRFs through the recently identified adaptor protein MAVS, a CARD domain containing protein that resides in the mitochondrial membrane. MAVS is essential for antiviral innate immunity, but it also serves as a target of Hepatitis C virus (HCV), which employs a viral protease to cleave MAVS off the mitochondria, thereby allowing HCV to escape the host immune system.
最近的研究发现了两条激活宿主针对病毒感染的固有免疫的信号通路。其中一条通路利用Toll样受体(TLR)家族的成员来检测通过内吞作用进入内体的病毒。TLR通路通过几种信号蛋白诱导干扰素产生,这些信号蛋白最终导致转录因子NF-κB、IRF3和IRF7的激活。另一条抗病毒通路使用RNA解旋酶RIG-I作为细胞内病毒双链RNA的受体。RIG-I通过最近鉴定出的接头蛋白MAVS激活NF-κB和IRF,MAVS是一种含有CARD结构域的蛋白,定位于线粒体膜。MAVS对抗病毒固有免疫至关重要,但它也是丙型肝炎病毒(HCV)的靶点,HCV利用一种病毒蛋白酶将MAVS从线粒体上切割下来,从而使HCV能够逃避宿主免疫系统。