Animal Infectious Disease Laboratory, School of Veterinary Medicine, College of Veterinary Medicine, Yangzhou University, 48 East Wenhui Road, Yangzhou, 225009, Jiangsu, China.
Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.
Arch Virol. 2018 Oct;163(10):2775-2786. doi: 10.1007/s00705-018-3926-3. Epub 2018 Jul 5.
Polymerase acidic (PA) protein is a multifunctional regulator of influenza A virus (IAV) replication and pathogenesis. In a previous study, we reported that nucleolin (NCL) is a novel PA-interacting host protein. In this study, we further explored the role of NCL during highly pathogenic H5N1 avian influenza virus infection. We found that depletion of endogenous NCL in mammalian cells by siRNA targeting during H5N1 infection resulted in significantly increased viral polymerase activity, elevated viral mRNA, cRNA and vRNA synthesis, accelerated viral replication, and enhanced apoptosis and necrosis. Moreover, siRNA silencing of NCL significantly exacerbated the inflammatory response, resulting in increased secretion of IL-6, TNF-α, TNF-β, CCL-4, CCL-8, IFN-α, IFN-β and IFN-γ. Conversely, overexpression of NCL significantly decreased IAV replication. Collectively, these data show that NCL acts as a novel potential antiviral factor during H5N1 infection. Further studies exploring the antiviral mechanisms of NCL may accelerate the development of new anti-influenza drugs.
聚合酶酸性（PA）蛋白是流感 A 病毒（IAV）复制和发病机制的多功能调节剂。在之前的研究中，我们报道核仁素（NCL）是一种新型的 PA 相互作用的宿主蛋白。在这项研究中，我们进一步探讨了 NCL 在高致病性 H5N1 禽流感病毒感染期间的作用。我们发现，在 H5N1 感染期间通过 siRNA 靶向内源性 NCL 的耗尽会导致病毒聚合酶活性显著增加，病毒 mRNA、cRNA 和 vRNA 合成增加，病毒复制加速，并增强细胞凋亡和坏死。此外，NCL 的 siRNA 沉默显著加剧了炎症反应，导致 IL-6、TNF-α、TNF-β、CCL-4、CCL-8、IFN-α、IFN-β 和 IFN-γ 的分泌增加。相反，NCL 的过表达显著降低了 IAV 的复制。总之，这些数据表明 NCL 在 H5N1 感染期间作为一种新型潜在的抗病毒因子发挥作用。进一步研究 NCL 的抗病毒机制可能会加速新的抗流感药物的开发。
