Beijing Key Laboratory for Prevention and Control of Infectious Diseases in Livestock and Poultry, Institute of Animal Husbandry and Veterinary Medicine, Beijing Academy of Agriculture and Forestry Sciences, Beijing, China.
College of Veterinary Medicine, Yangzhou Universitygrid.268415.c, Yangzhou, Jiangsu Province, China.
Microbiol Spectr. 2022 Apr 27;10(2):e0030422. doi: 10.1128/spectrum.00304-22. Epub 2022 Mar 31.
Seneca Valley virus (SVV) is a recently discovered pathogen that poses a significant threat to the global pig industry. It has been shown that many viruses are reliant on nucleocytoplasmic trafficking of nucleolin (NCL) for their own replication. Here, we demonstrate that NCL, a critical protein component of the nucleolus, is cleaved and translocated out of the nucleoli following SVV infection. Furthermore, our data suggest that SVV 3C protease (3C) is responsible for this cleavage and subsequent delocalization from the nucleoli, and that inactivation of this protease activity abolished this cleavage and translocation. SVV 3C cleaved NCL at residue Q545, and the cleavage fragment (aa 1 to 545) facilitated viral replication, which was similar to the activities described for full-length NCL. Small interfering RNA-mediated knockdown indicated that NCL is required for efficient viral replication and viral protein expression. In contrast, lentivirus-mediated overexpression of NCL significantly enhanced viral replication. Taken together, these results indicate that SVV 3C targets NCL for its cleavage and redistribution, which contributes to efficient viral replication, thereby emphasizing the potential target of antiviral strategies for the control of SVV infection. The nucleolus is a subnuclear cellular compartment, and nucleolin (NCL) resides predominantly in the nucleolus. NCL participates in viral replication, translation, internalization, and also serves as a receptor for virus entry. The interaction between NCL and SVV is still unknown. Here, we demonstrate that SVV 3C targets NCL for its cleavage and nucleocytoplasmic transportation, which contributes to efficient viral replication. Our results reveal novel function of SVV 3C and provide further insight into the mechanisms by which SVV utilizes nucleoli for efficient replication.
毫华病毒 (SVV) 是一种新近发现的病原体，对全球养猪业构成重大威胁。研究表明，许多病毒依赖核质运输核仁素 (NCL) 来进行自身复制。在这里，我们证明 NCL，即核仁的关键蛋白组成部分，在 SVV 感染后被切割并从核仁中转位。此外，我们的数据表明，SVV 3C 蛋白酶 (3C) 负责这种切割和随后从核仁中的去定位，并且该蛋白酶活性的失活会阻止这种切割和转位。SVV 3C 在残基 Q545 处切割 NCL，切割片段 (aa1 至 545) 促进病毒复制，这与全长 NCL 所描述的活性相似。小干扰 RNA 介导的敲低表明 NCL 是病毒有效复制和病毒蛋白表达所必需的。相比之下，慢病毒介导的 NCL 过表达显著增强了病毒复制。总之，这些结果表明 SVV 3C 靶向 NCL 进行切割和重新分布，这有助于病毒的有效复制，从而强调了针对 SVV 感染的抗病毒策略的潜在靶点。核仁是亚核细胞区室，核仁素 (NCL) 主要存在于核仁中。NCL 参与病毒复制、翻译、内化，并且也是病毒进入的受体。NCL 与 SVV 之间的相互作用仍然未知。在这里，我们证明 SVV 3C 靶向 NCL 进行切割和核质运输，这有助于病毒的有效复制。我们的结果揭示了 SVV 3C 的新功能，并进一步深入了解 SVV 利用核仁进行高效复制的机制。
