A Potential Role for Substance P in West Nile Virus Neuropathogenesis

Authors

Shannon E Ronca
Sarah M Gunter
Rebecca Berry Kairis
Allison Lino
Jonathan Romero
Robia G Pautler
Alan Nimmo
Kristy O Murray

Publication Date

9-4-2022

Journal

Viruses

DOI

10.3390/v14091961

PMID

36146768

PMCID

PMC9503494

PubMedCentral® Posted Date

9-4-2022

PubMedCentral® Full Text Version

Post-print

Published Open-Access

yes

Keywords

Animals, Brain, Mice, Pilot Projects, Substance P, West Nile Fever, West Nile virus, West Nile virus, substance P, neurokinin-1 receptor, neuroinflammation, West Nile encephalitis

Abstract

Of individuals who develop West Nile neuroinvasive disease (WNND), ~10% will die and >40% will develop long-term complications. Current treatment recommendations solely focus on supportive care; therefore, we urgently need to identify novel and effective therapeutic options. We observed a correlation between substance P (SP), a key player in neuroinflammation, and its receptor Neurokinin-1 (NK1R). Our study in a wild-type BL6 mouse model found that SP is upregulated in the brain during infection, which correlated with neuroinvasion and damage to the blood−brain barrier. Blocking the SP/NK1R interaction beginning at disease onset modestly improved survival and prolonged time to death in a small pilot study. Although SP is significantly increased in the brain of untreated WNND mice when compared to mock-infected animals, levels of WNV are unchanged, indicating that SP likely does not play a role in viral replication but may mediate the immune response to infection. Additional studies are necessary to define if SP plays a mechanistic role or if it represents other mechanistic pathways.