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.