PDF(Pubmed)
Abstract：
The pseudorabies virus (PRV) is identified as a double-helical DNA virus responsible for causing Aujeszky\'s disease, which results in considerable economic impacts globally. The enzyme tryptophanyl-tRNA synthetase 2 (WARS2), a mitochondrial protein involved in protein synthesis, is recognized for its broad expression and vital role in the translation process. The findings of our study showed an increase in both mRNA and protein levels of WARS2 following PRV infection in both cell cultures and animal models. Suppressing WARS2 expression via RNA interference in PK-15 cells led to a reduction in PRV infection rates, whereas enhancing WARS2 expression resulted in increased infection rates. Furthermore, the activation of WARS2 in response to PRV was found to be reliant on the cGAS/STING/TBK1/IRF3 signaling pathway and the interferon-alpha receptor-1, highlighting its regulation via the type I interferon signaling pathway. Further analysis revealed that reducing WARS2 levels hindered PRV\'s ability to promote protein and lipid synthesis. Our research provides novel evidence that WARS2 facilitates PRV infection through its management of protein and lipid levels, presenting new avenues for developing preventative and therapeutic measures against PRV infections.
摘要：
伪狂犬病病毒（PRV）被认为是导致Aujeszky病的双螺旋DNA病毒，这导致了全球相当大的经济影响。色氨酸-tRNA合成酶2（WARS2），参与蛋白质合成的线粒体蛋白质，其广泛的表达和在翻译过程中的重要作用是公认的。我们的研究结果表明，在细胞培养和动物模型中，PRV感染后WARS2的mRNA和蛋白质水平均增加。通过RNA干扰抑制PK-15细胞中的WARS2表达导致PRV感染率降低,而增强WARS2表达导致感染率增加。此外，发现响应PRV的WARS2激活依赖于cGAS/STING/TBK1/IRF3信号通路和干扰素-α受体-1,突出了其通过I型干扰素信号通路的调节.进一步的分析表明，降低WARS2水平阻碍了PRV促进蛋白质和脂质合成的能力。我们的研究提供了新的证据，表明WARS2通过其蛋白质和脂质水平的管理促进PRV感染，为开发针对PRV感染的预防和治疗措施提供了新的途径。
