Division of Molecular Pathobiology, Hokkaido University Research Center for Zoonosis Control, Hokkaido University, Sapporo, Japan.
Neuropathology. 2012 Aug;32(4):398-405. doi: 10.1111/j.1440-1789.2011.01275.x. Epub 2011 Dec 1.
West Nile virus (WNV) belongs to the Flaviviridae family of viruses and has emerged as a significant cause of viral encephalitis in humans, animals and birds. It has been reported that WNV replication directly induces neuronal injury, followed by neuronal cell death proven as apoptosis. Therefore, it is important to understand the mechanism of neuronal apoptosis caused by this virus to develop strategies to control its pathogenicity. Accumulation of ubiquitinated abnormal proteins has been reported to be associated with neuronal apoptosis in some pathological conditions. A lot of cellular stresses prevent cellular protein quality control mechanisms, resulting in the accumulation of ubiquitinated abnormal proteins. To obtain a better understanding of the mechanisms of WNV-induced neuronal apoptosis, we evaluated the accumulation of ubiquitinated proteins in the WNV-infected neuronal cells. We have observed that WNV infection caused massive neuronal injury in the brains of mice. Viral antigen was detected in the neuronal cytoplasm of the cells exhibiting neuronal apoptosis. Notably, ubiquitinated proteins were detected in WNV-infected neuronal cells. In addition, accumulation of ubiquitinated proteins was markedly enhanced in mouse neuroblastoma, Neuro-2a cells after WNV infection. Our histopathological and in vitro studies suggest that accumulation of ubiquitinated proteins in neuronal cells might be associated with neuronal apoptosis caused by WNV infection.
西尼罗河病毒（WNV）属于黄病毒科病毒，已成为人类、动物和鸟类病毒性脑炎的重要病因。据报道，WNV 复制可直接诱导神经元损伤，随后通过凋亡证实神经元细胞死亡。因此，了解该病毒引起的神经元凋亡的机制对于开发控制其致病性的策略非常重要。在某些病理条件下，已报道异常积聚的泛素化蛋白与神经元凋亡有关。大量细胞应激会阻止细胞蛋白质量控制机制，导致泛素化异常蛋白的积累。为了更好地了解 WNV 诱导的神经元凋亡的机制，我们评估了 WNV 感染神经元细胞中泛素化蛋白的积累。我们观察到 WNV 感染会导致小鼠大脑中大量神经元损伤。在表现出神经元凋亡的细胞的神经元细胞质中检测到病毒抗原。值得注意的是，WNV 感染的神经元细胞中检测到泛素化蛋白。此外，WNV 感染后，鼠神经母细胞瘤、Neuro-2a 细胞中泛素化蛋白的积累明显增加。我们的组织病理学和体外研究表明，神经元细胞中泛素化蛋白的积累可能与 WNV 感染引起的神经元凋亡有关。
