Xue Qiao, Liu Huisheng, Zhu Zixiang, Xue Zhaoning, Liu Xiangtao, Zheng Haixue
State Key Laboratory of Veterinary Etiological Biology, National Foot and Mouth Diseases Reference Laboratory, Key Laboratory of Animal Virology of Ministry of Agriculture, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou 730046, China.
Pathogens. 2020 Jun 4;9(6):443. doi: 10.3390/pathogens9060443.
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 induced the cleavage of PABPC1 by its protease activity. The SVV strains with inactive point mutants of 3C (H48A, C160A or H48A/C160A) can not be rescued by reverse genetics, suggesting that sites 48 and 160 of 3C were essential for SVV replication. SVV 3C induced the cleavage of PABPC1 at residue 437. A detailed data analysis showed that SVV infection and the overexpression of 3C decreased the protein synthesis rates. The protease activity of 3C 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 on SVV replication.
塞内卡山谷病毒（SVV）是近年来出现的一种属于小核糖核酸病毒科的溶瘤病毒。SVV对宿主细胞翻译的影响尚不清楚。在此，我们首次表明，SVV感染会切割聚腺苷酸结合蛋白胞质1（PABPC1）。在SVV感染的细胞中，检测到PABPC1的50 kDa N端切割带和25 kDa C端切割带。进一步研究表明，病毒蛋白酶3C通过其蛋白酶活性诱导PABPC1的切割。具有3C无活性点突变体（H48A、C160A或H48A/C160A）的SVV毒株无法通过反向遗传学拯救，这表明3C的48位和160位位点对SVV复制至关重要。SVV 3C在437位残基处诱导PABPC1的切割。详细的数据分析表明，SVV感染和3C的过表达降低了蛋白质合成速率。3C的蛋白酶活性对于抑制蛋白质合成至关重要。我们的结果还表明，PABPC1抑制SVV复制。这些数据揭示了一种由SVV介导的新型拮抗机制和发病机制，并突出了3C对SVV复制的重要性。
