A Potential Role for Substance P in West Nile Virus Neuropathogenesis
Journal Publication ResearchOnline@JCUAbstract
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.
Journal
Viruses
Publication Name
N/A
Volume
14
ISBN/ISSN
1999-4915
Edition
N/A
Issue
9
Pages Count
12
Location
N/A
Publisher
MDPI
Publisher Url
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Publisher Location
N/A
Publish Date
N/A
Url
N/A
Date
N/A
EISSN
N/A
DOI
10.3390/v14091961