دورية أكاديمية
Eastern equine encephalitis virus rapidly infects and disseminates in the brain and spinal cord of cynomolgus macaques following aerosol challenge.
| العنوان: | Eastern equine encephalitis virus rapidly infects and disseminates in the brain and spinal cord of cynomolgus macaques following aerosol challenge. |
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| المؤلفون: | Janice A Williams, Simon Y Long, Xiankun Zeng, Kathleen Kuehl, April M Babka, Neil M Davis, Jun Liu, John C Trefry, Sharon Daye, Paul R Facemire, Patrick L Iversen, Sina Bavari, Margaret L Pitt, Farooq Nasar |
| المصدر: | PLoS Neglected Tropical Diseases, Vol 16, Iss 5, p e0010081 (2022) |
| بيانات النشر: | Public Library of Science (PLoS), 2022. |
| سنة النشر: | 2022 |
| المجموعة: | LCC:Arctic medicine. Tropical medicine LCC:Public aspects of medicine |
| مصطلحات موضوعية: | Arctic medicine. Tropical medicine, RC955-962, Public aspects of medicine, RA1-1270 |
| الوصف: | Eastern equine encephalitis virus (EEEV) is mosquito-borne virus that produces fatal encephalitis in humans. We recently conducted a first of its kind study to investigate EEEV clinical disease course following aerosol challenge in a cynomolgus macaque model utilizing the state-of-the-art telemetry to measure critical physiological parameters. Here, we report the results of a comprehensive pathology study of NHP tissues collected at euthanasia to gain insights into EEEV pathogenesis. Viral RNA and proteins as well as microscopic lesions were absent in the visceral organs. In contrast, viral RNA and proteins were readily detected throughout the brain including autonomic nervous system (ANS) control centers and spinal cord. However, despite presence of viral RNA and proteins, majority of the brain and spinal cord tissues exhibited minimal or no microscopic lesions. The virus tropism was restricted primarily to neurons, and virus particles (~61-68 nm) were present within axons of neurons and throughout the extracellular spaces. However, active virus replication was absent or minimal in majority of the brain and was limited to regions proximal to the olfactory tract. These data suggest that EEEV initially replicates in/near the olfactory bulb following aerosol challenge and is rapidly transported to distal regions of the brain by exploiting the neuronal axonal transport system to facilitate neuron-to-neuron spread. Once within the brain, the virus gains access to the ANS control centers likely leading to disruption and/or dysregulation of critical physiological parameters to produce severe disease. Moreover, the absence of microscopic lesions strongly suggests that the underlying mechanism of EEEV pathogenesis is due to neuronal dysfunction rather than neuronal death. This study is the first comprehensive investigation into EEEV pathology in a NHP model and will provide significant insights into the evaluation of countermeasure. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1935-2727 1935-2735 |
| Relation: | https://doaj.org/toc/1935-2727; https://doaj.org/toc/1935-2735 |
| DOI: | 10.1371/journal.pntd.0010081 |
| URL الوصول: | https://doaj.org/article/e0025dac2e08438583ecc1f56d0b2178 |
| رقم الأكسشن: | edsdoj.0025dac2e08438583ecc1f56d0b2178 |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 19352727 19352735 |
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| DOI: | 10.1371/journal.pntd.0010081 |