Department of Microbiology and Molecular Genetics, School of Medicine, University of California, Irvine, California, USA.
J Virol. 2014 Mar;88(6):3192-201. doi: 10.1128/JVI.02503-13. Epub 2013 Dec 26.
Due to their small genome size, picornaviruses must utilize host proteins to mediate cap-independent translation and viral RNA replication. The host RNA-binding protein poly(rC) binding protein 2 (PCBP2) is involved in both processes in poliovirus infected cells. It has been shown that the viral proteinase 3CD cleaves PCBP2 and contributes to viral translation inhibition. However, cleaved PCBP2 remains active in viral RNA replication. This would suggest that both cleaved and intact forms of PCBP2 have a role in the viral RNA replication cycle. The picornavirus genome must act as a template for both translation and RNA replication. However, a template that is actively being translated cannot function as a template for RNA replication, suggesting that there is a switch in template usage from translation to RNA replication. We demonstrate that the cleavage of PCBP2 by the poliovirus 3CD proteinase is a necessary step for efficient viral RNA replication and, as such, may be important for mediating a switch in template usage from translation to RNA replication.
Poliovirus, like all positive-strand RNA viruses that replicate in the cytoplasm of eukaryotic cells, uses its genomic RNA as a template for both viral protein synthesis and RNA replication. Given that these processes cannot occur simultaneously on the same template, poliovirus has evolved a mechanism(s) to facilitate the switch from using templates for translation to using them for RNA synthesis. This study explores one possible scenario for how the virus alters the functions of a host cell RNA binding protein to mediate, in part, this important transition.
由于小基因组大小，小 RNA 病毒必须利用宿主蛋白来介导帽非依赖性翻译和病毒 RNA 复制。宿主 RNA 结合蛋白多聚（rC）结合蛋白 2（PCBP2）参与了脊髓灰质炎病毒感染细胞中的这两个过程。已经表明，病毒蛋白酶 3CD 切割 PCBP2 并有助于病毒翻译抑制。然而，切割的 PCBP2 在病毒 RNA 复制中仍然保持活性。这表明切割和完整形式的 PCBP2 在病毒 RNA 复制周期中都有作用。小 RNA 病毒基因组必须作为翻译和 RNA 复制的模板。然而，正在被翻译的模板不能作为 RNA 复制的模板，这表明模板的使用从翻译到 RNA 复制发生了转换。我们证明了脊髓灰质炎病毒 3CD 蛋白酶对 PCBP2 的切割是病毒 RNA 复制的有效步骤，因此可能对介导从翻译到 RNA 复制的模板使用转换很重要。
脊髓灰质炎病毒，就像所有在真核细胞细胞质中复制的正链 RNA 病毒一样，将其基因组 RNA 用作病毒蛋白合成和 RNA 复制的模板。鉴于这些过程不能在同一模板上同时发生，脊髓灰质炎病毒已经进化出一种机制（多种机制）来促进从使用模板进行翻译到使用模板进行 RNA 合成的转换。本研究探讨了病毒改变宿主细胞 RNA 结合蛋白的功能以介导这一重要转变的一种可能情况。
