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A Potential Role for Substance P in West Nile Virus Neuropathogenesis
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 correla...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503494/ https://www.ncbi.nlm.nih.gov/pubmed/36146768 http://dx.doi.org/10.3390/v14091961 |
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author | Ronca, Shannon E. Gunter, Sarah M. Kairis, Rebecca Berry Lino, Allison Romero, Jonathan Pautler, Robia G. Nimmo, Alan Murray, Kristy O. |
author_facet | Ronca, Shannon E. Gunter, Sarah M. Kairis, Rebecca Berry Lino, Allison Romero, Jonathan Pautler, Robia G. Nimmo, Alan Murray, Kristy O. |
author_sort | Ronca, Shannon E. |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-9503494 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-95034942022-09-24 A Potential Role for Substance P in West Nile Virus Neuropathogenesis Ronca, Shannon E. Gunter, Sarah M. Kairis, Rebecca Berry Lino, Allison Romero, Jonathan Pautler, Robia G. Nimmo, Alan Murray, Kristy O. Viruses Article 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. MDPI 2022-09-04 /pmc/articles/PMC9503494/ /pubmed/36146768 http://dx.doi.org/10.3390/v14091961 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Ronca, Shannon E. Gunter, Sarah M. Kairis, Rebecca Berry Lino, Allison Romero, Jonathan Pautler, Robia G. Nimmo, Alan Murray, Kristy O. A Potential Role for Substance P in West Nile Virus Neuropathogenesis |
title | A Potential Role for Substance P in West Nile Virus Neuropathogenesis |
title_full | A Potential Role for Substance P in West Nile Virus Neuropathogenesis |
title_fullStr | A Potential Role for Substance P in West Nile Virus Neuropathogenesis |
title_full_unstemmed | A Potential Role for Substance P in West Nile Virus Neuropathogenesis |
title_short | A Potential Role for Substance P in West Nile Virus Neuropathogenesis |
title_sort | potential role for substance p in west nile virus neuropathogenesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9503494/ https://www.ncbi.nlm.nih.gov/pubmed/36146768 http://dx.doi.org/10.3390/v14091961 |
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