Abstract

Viruses exploit the translation machinery of an infected cell to synthesize their proteins. Therefore, viral mRNAs have to compete for ribosomes and translation factors with cellular mRNAs. To succeed, eukaryotic viruses adopt multiple strategies. One is to circumvent the need for m⁷G-cap through alternative instruments for ribosome recruitment. These include internal ribosome entry sites (IRESs), which make translation independent of the free 5′ end, or cap-independent translational enhancers (CITEs), which promote initiation at the uncapped 5′ end, even if located in 3′ untranslated regions (3′ UTRs). Even if a virus uses the canonical cap-dependent ribosome recruitment, it can still perturb conventional ribosomal scanning and start codon selection. The pressure for genome compression often gives rise to internal and overlapping open reading frames. Their translation is initiated through specific mechanisms, such as leaky scanning, 43S sliding, shunting, or coupled termination-reinitiation. Deviations from the canonical initiation reduce the dependence of viral mRNAs on translation initiation factors, thereby providing resistance to antiviral mechanisms and cellular stress responses. Moreover, viruses can gain advantage in a competition for the translational machinery by inactivating individual translational factors and/or replacing them with viral counterparts. Certain viruses even create specialized intracellular “translation factories”, which spatially isolate the sites of their protein synthesis from cellular antiviral systems, and increase availability of translational components. However, these virus-specific mechanisms may become the Achilles’ heel of a viral life cycle. Thus, better understanding of the unconventional mechanisms of viral mRNA translation initiation provides valuable insight for developing new approaches to antiviral therapy.

中文翻译：

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真核病毒 mRNA 采用的非规范翻译起始机制

摘要

病毒利用受感染细胞的翻译机制来合成蛋白质。因此，病毒mRNA必须与细胞mRNA竞争核糖体和翻译因子。为了成功，真核病毒采用多种策略。一是通过替代核糖体招募工具来避免对 m ⁷ G-cap的需要。这些包括内部核糖体进入位点 (IRES)，它使翻译独立于游离 5' 末端，或不依赖帽的翻译增强子 (CITE)，它促进在无帽 5' 末端的起始，即使位于 3' 非翻译区域。 3' UTR）。即使病毒使用规范的帽依赖性核糖体招募，它仍然可以扰乱传统的核糖体扫描并开始密码子选择。基因组压缩的压力常常会产生内部和重叠的开放阅读框。它们的翻译是通过特定机制启动的，例如泄漏扫描、43S 滑动、分流或耦合终止-重新启动。偏离规范起始可减少病毒 mRNA 对翻译起始因子的依赖性，从而提供对抗病毒机制和细胞应激反应的抵抗力。此外，病毒可以通过灭活单个翻译因子和/或用病毒对应物替换它们来在翻译机制的竞争中获得优势。某些病毒甚至会创建专门的细胞内“翻译工厂”，在空间上将其蛋白质合成位点与细胞抗病毒系统隔离，并增加翻译组件的可用性。然而，这些病毒特异性机制可能成为病毒生命周期的致命弱点。因此，更好地了解病毒 mRNA 翻译起始的非常规机制为开发新的抗病毒治疗方法提供了宝贵的见解。