Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China.
Institute of Veterinary Medicine, Jiangsu Academy of Agricultural Sciences, Key Laboratory of Veterinary Biological Engineering and Technology, Ministry of Agriculture, National Center for Engineering Research of Veterinary Bio-products, Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, PR China.
Microb Pathog. 2019 Jul;132:362-368. doi: 10.1016/j.micpath.2019.04.044. Epub 2019 May 1.
Duck Tembusu virus (DTMUV) is a newly emerging pathogenic flavivirus that has caused massive economic losses to the duck industry in China. The cellular factors required for DTMUV replication have been poorly studied. The ubiquitin-proteasome system (UPS), the major intracellular proteolytic pathway, mediates diverse cellular processes, including endocytosis and signal transduction, which may be involved in the entry of virus. In the present study, we explored the interplay between DTMUV replication and the UPS in BHK-21 cells and found that treatment with proteasome inhibitor (MG132 and lactacystin) significantly decreased the DTMUV progency at the early infection stage. We further revealed that inhibition of the UPS mainly occurs on the level of viral protein expression and RNA transcription. In addition, using specific siRNAs targeting ubiquitin reduces the production of viral progeny. In the presence of MG132 the staining for the envelope protein of DTMUV was dramatically reduced in comparison with the untreated control cells. Overall, our observations reveal an important role of the UPS in multiple steps of the DTMUV infection cycle and identify the UPS as a potential drug target to modulate the impact of DTMUV infection.
鸭坦布苏病毒（DTMUV）是一种新兴的致病性黄病毒，已给中国养鸭业造成巨大的经济损失。对于 DTMUV 复制所需的细胞因子研究甚少。泛素-蛋白酶体系统（UPS）是主要的细胞内蛋白水解途径，介导包括内吞作用和信号转导在内的多种细胞过程，这些过程可能参与了病毒的进入。在本研究中，我们探索了 BHK-21 细胞中 DTMUV 复制与 UPS 之间的相互作用，发现蛋白酶体抑制剂（MG132 和 lactacystin）处理可显著降低早期感染阶段的 DTMUV 后代。我们进一步揭示抑制 UPS 主要发生在病毒蛋白表达和 RNA 转录水平上。此外，使用针对泛素的特异性 siRNA 可减少病毒产物的产生。在 MG132 的存在下，与未处理的对照细胞相比，DTMUV 的包膜蛋白染色显著减少。总之，我们的观察结果揭示了 UPS 在 DTMUV 感染周期的多个步骤中起着重要作用，并将 UPS 确定为调节 DTMUV 感染影响的潜在药物靶点。
