Seneca Valley Virus 3Cpro Cleaves PABPC1 to Promote Viral Replication
Seneca Valley Virus 3Cpro Cleaves PABPC1 to Promote Viral Replication
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DOI：
10.3390/pathogens9060443
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发表时间：
2020-06-01
期刊：
影响因子：
3.7
通讯作者：
Zheng, Haixue
中科院分区：
文献类型：
--
作者：
Xue, Qiao;Liu, Huisheng;Zheng, Haixue
塞内卡谷病毒（Seneca Valley Virus，SVV）是近年来出现的小核糖核酸病毒科的溶瘤病毒。SVV对宿主细胞翻译的影响仍然未知。在这里，我们首次表明，SVV感染裂解多聚腺苷酸结合蛋白胞质1（PABPC 1）。在SVV感染的细胞中，检测到PABPC 1的N端切割带的50 kDa和C端切割带的25 kDa。进一步的研究表明，病毒蛋白酶3C（pro）通过其蛋白酶活性诱导PABPC 1的切割。3C（pro）位点失活突变体（H48 A、C160 A或H48 A/C160 A）不能被反向遗传学拯救，表明3C（pro）位点48和160是SVV复制所必需的。SVV 3C（pro）诱导PABPC 1在残基437处裂解。详细的数据分析表明，SVV感染和3C（pro）的过表达降低了蛋白质合成速率。3C（pro）的蛋白酶活性是抑制蛋白质合成所必需的。我们的结果还表明PABPC 1抑制SVV复制。这些数据揭示了SVV介导的一种新的拮抗机制和发病机制，并强调了3C（pro）对SVV复制的重要性。
Seneca Valley Virus (SVV) is an oncolytic virus of the Picornaviridae family, which has emerged in recent years. The impact of SVV on host cell translation remains unknown. Here, we showed, for the first time, that SVV infection cleaved poly(A) binding protein cytoplasmic 1 (PABPC1). In SVV-infected cells, 50 kDa of the N terminal cleaved band and 25 kDa of the C terminal cleaved band of PABPC1 were detected. Further study showed that the viral protease, 3C(pro) induced the cleavage of PABPC1 by its protease activity. The SVV strains with inactive point mutants of 3C(pro) (H48A, C160A or H48A/C160A) can not be rescued by reverse genetics, suggesting that sites 48 and 160 of 3C(pro) were essential for SVV replication. SVV 3C(pro) induced the cleavage of PABPC1 at residue 437. A detailed data analysis showed that SVV infection and the overexpression of 3C(pro) decreased the protein synthesis rates. The protease activity of 3C(pro) was essential for inhibiting the protein synthesis. Our results also indicated that PABPC1 inhibited SVV replication. These data reveal a novel antagonistic mechanism and pathogenesis mediated by SVV and highlight the importance of 3C(pro) on SVV replication.