Sen G C
Department of Molecular Biology, Lerner Research Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44195, USA.
Annu Rev Microbiol. 2001;55:255-81. doi: 10.1146/annurev.micro.55.1.255.
The interferon system is the first line of defense against viral infection in mammals. This system is designed to block the spread of virus infection in the body, sometimes at the expense of accelerating the death of the infected cells. As expected of potent cytokines, in addition to their antiviral effects, interferons have profound effects on many aspects of cell physiology. All these actions of interferons are mediated by hundreds of interferon-induced proteins that are usually not synthesized in resting cells. Interferons induce their synthesis by activating the Jak-STAT pathways, a paradigm of cell signaling used by many cytokines and growth factors. Surprisingly, some of the same genes can also be induced directly by viruses and double-stranded RNA, a common viral by-product. Some of the interferon-induced proteins have novel biochemical properties and some are inactive as such but can be activated by double-stranded RNA produced during virus infection. Finally, almost all viruses have evolved mechanisms to evade the interferon system by partially blocking interferon synthesis or interferon action. Thus, in nature interferons and viruses maintain an equilibrium that allows regulated viral replication.
干扰素系统是哺乳动物抵御病毒感染的第一道防线。该系统旨在阻止病毒感染在体内的传播,有时是以加速受感染细胞的死亡为代价。正如强效细胞因子所预期的那样,除了具有抗病毒作用外,干扰素对细胞生理学的许多方面都有深远影响。干扰素的所有这些作用都是由数百种干扰素诱导蛋白介导的,这些蛋白通常不在静息细胞中合成。干扰素通过激活Jak-STAT信号通路来诱导它们的合成,Jak-STAT信号通路是许多细胞因子和生长因子所使用的一种细胞信号传导模式。令人惊讶的是,一些相同的基因也可以直接由病毒和双链RNA(一种常见的病毒副产物)诱导。一些干扰素诱导蛋白具有新颖的生化特性,有些本身无活性,但可被病毒感染期间产生的双链RNA激活。最后,几乎所有病毒都进化出了通过部分阻断干扰素合成或干扰素作用来逃避干扰素系统的机制。因此,在自然界中,干扰素和病毒维持着一种平衡,使得病毒复制得以调控。