Gale M, Tan S L, Katze M G
University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Microbiol Mol Biol Rev. 2000 Jun;64(2):239-80. doi: 10.1128/MMBR.64.2.239-280.2000.
As obligate intracellular parasites, viruses rely exclusively on the translational machinery of the host cell for the synthesis of viral proteins. This relationship has imposed numerous challenges on both the infecting virus and the host cell. Importantly, viruses must compete with the endogenous transcripts of the host cell for the translation of viral mRNA. Eukaryotic viruses have thus evolved diverse mechanisms to ensure translational efficiency of viral mRNA above and beyond that of cellular mRNA. Mechanisms that facilitate the efficient and selective translation of viral mRNA may be inherent in the structure of the viral nucleic acid itself and can involve the recruitment and/or modification of specific host factors. These processes serve to redirect the translation apparatus to favor viral transcripts, and they often come at the expense of the host cell. Accordingly, eukaryotic cells have developed antiviral countermeasures to target the translational machinery and disrupt protein synthesis during the course of virus infection. Not to be outdone, many viruses have answered these countermeasures with their own mechanisms to disrupt cellular antiviral pathways, thereby ensuring the uncompromised translation of virion proteins. Here we review the varied and complex translational programs employed by eukaryotic viruses. We discuss how these translational strategies have been incorporated into the virus life cycle and examine how such programming contributes to the pathogenesis of the host cell.
作为专性细胞内寄生虫,病毒完全依赖宿主细胞的翻译机制来合成病毒蛋白。这种关系给感染病毒和宿主细胞都带来了诸多挑战。重要的是,病毒必须与宿主细胞的内源性转录本竞争病毒mRNA的翻译。因此,真核病毒进化出了多种机制,以确保病毒mRNA的翻译效率高于细胞mRNA。促进病毒mRNA高效和选择性翻译的机制可能内在地存在于病毒核酸本身的结构中,并且可能涉及特定宿主因子的募集和/或修饰。这些过程旨在使翻译装置转向有利于病毒转录本,并且它们常常以宿主细胞为代价。相应地,真核细胞已经开发出抗病毒对策,以在病毒感染过程中靶向翻译机制并破坏蛋白质合成。许多病毒也不甘示弱,通过自身机制应对这些对策,破坏细胞抗病毒途径,从而确保病毒粒子蛋白的翻译不受影响。在此,我们综述真核病毒采用的多样且复杂的翻译程序。我们讨论这些翻译策略如何被纳入病毒生命周期,并研究这种程序设计如何促成宿主细胞的发病机制。