West Nile virus NS1 Antigen ELISA Kit

The E3 ubiquitin ligase Pellino 1 (Peli1) is a microglia-specific mediator of autoimmune encephalomyelitis. Its role in neurotropic flavivirus infection is largely unknown. Here, we report that mice deficient in Peli1 (Peli1(-/-)) were more resistant to lethal West Nile virus (WNV) infection and exhibited reduced viral loads in tissues and attenuated brain inflammation. Peli1 mediates chemokine and proinflammatory cytokine production in microglia and promotes T cell and macrophage infiltration into the CNS. Unexpectedly, Peli1 was required for WNV entry and replication in mouse macrophages and mouse and human neurons and microglia. It was also highly expressed on WNV-infected neurons and adjacent inflammatory cells from postmortem patients who died of acute WNV encephalitis. WNV passaged in Peli1(-/-) macrophages or neurons induced a lower viral load and impaired activation in WT microglia and thereby reduced lethality in mice. Smaducin-6, which blocks interactions between Peli1 and IRAK1, RIP1, and IKK epsilon, did not inhibit WNV-triggered microglia activation. Collectively, our findings suggest a nonimmune regulatory role for Peli1 in promoting microglia activation during WNV infection and identify a potentially novel host factor for flavivirus cell entry and replication.

West Nile virus (WNV) is an arthropod-borne flavivirus belonging taxonomically to the Japanese encephalitis subgroup. Usually, it is transmitted by Culex pipiens mosquitoes. Consequently, an increase in WNV-positive mosquitoes presents a rise of the number of patients, as it has been seen in NYC. We present a 65-year-old patient with WNV infection who presented with Guillain-Barre syndrome (GBS). She had a rapidly progressing ascending paralysis, a common feature in GBS patients but an uncommon presentation in WNV. Realizing WNV as an emerging pathogen along with its uncommon presentation of GBS can be potentially lifesaving if caught at an early stage.