Expression of flavivirus capsids enhance the cellular environment for viral replication by activating Akt-signalling pathways.

Flaviviruses depend on multiple host pathways during their life cycles and have evolved strategies to avoid the innate immune response. Previously, we showed that the West Nile virus capsid protein plays a role in this process by blocking apoptosis. In this study, we examined how expression of capsid proteins from several flaviviruses affects apoptosis and other host processes that impact virus replication.

The West Nile virus capsid protein blocks apoptosis through a phosphatidylinositol 3-kinase-dependent mechanism.

West Nile virus (WNV) is a mosquito-transmitted pathogen that can cause serious disease in humans. Our laboratories are focused on understanding how interactions between WNV proteins and host cells contribute to virus replication and pathogenesis. WNV replication is relatively slow, and on the basis of earlier studies, the virus appears to activate survival pathways that delay host cell death during virus replication.

West Nile virus infection causes endocytosis of a specific subset of tight junction membrane proteins.

West Nile virus (WNV) is a blood-borne pathogen that causes systemic infections and serious neurological disease in human and animals. The most common route of infection is mosquito bites and therefore, the virus must cross a number of polarized cell layers to gain access to organ tissue and the central nervous system. Resistance to trans-cellular movement of macromolecules between epithelial and endothelial cells is mediated by tight junction complexes.

West Nile virus-induced neuroinflammation: glial infection and capsid protein-mediated neurovirulence.

West Nile virus (WNV) infection causes neurological disease at all levels of the neural axis, accompanied by neuroinflammation and neuronal loss, although the underlying mechanisms remain uncertain. Given the substantial activation of neuroinflammatory pathways observed in WNV infection, we hypothesized that WNV-mediated neuroinflammation and cell death occurred through WNV infection of both glia and neurons, which was driven in part by WNV capsid protein expression. Analysis of autopsied neural tissues from humans with WNV encephalomyelitis (WNVE) revealed WNV infection of both neurons and glia.