Figure 8. Proposed model illustrating how Peli1 promotes virus replication and neuroinflammation during WNV infection.

In the periphery, Peli1 promotes WNV replication in macrophages and DCs and positively regulates antiviral innate immune responses in these cells. Peli1 also negatively mediates IFN-γ production in T cells. Once the virus crosses the BBB and enters the CNS, Peli1 facilitates WNV replication in microglia and neurons and further boosts a robust inflammatory cytokine and chemokine production in these cells, which attracts more inflammatory cells infiltrated from the periphery and ultimately contributes to lethal WNV encephalitis.