In:
PLOS Neglected Tropical Diseases, Public Library of Science (PLoS), Vol. 16, No. 5 ( 2022-5-9), p. e0010081-
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
1935-2735
DOI:
10.1371/journal.pntd.0010081
DOI:
10.1371/journal.pntd.0010081.g001
DOI:
10.1371/journal.pntd.0010081.g002
DOI:
10.1371/journal.pntd.0010081.g003
DOI:
10.1371/journal.pntd.0010081.g004
DOI:
10.1371/journal.pntd.0010081.g005
DOI:
10.1371/journal.pntd.0010081.g006
DOI:
10.1371/journal.pntd.0010081.g007
DOI:
10.1371/journal.pntd.0010081.g008
DOI:
10.1371/journal.pntd.0010081.g009
DOI:
10.1371/journal.pntd.0010081.g010
DOI:
10.1371/journal.pntd.0010081.g011
DOI:
10.1371/journal.pntd.0010081.g012
DOI:
10.1371/journal.pntd.0010081.g013
DOI:
10.1371/journal.pntd.0010081.g014
DOI:
10.1371/journal.pntd.0010081.g015
DOI:
10.1371/journal.pntd.0010081.g016
DOI:
10.1371/journal.pntd.0010081.g017
DOI:
10.1371/journal.pntd.0010081.g018
DOI:
10.1371/journal.pntd.0010081.g019
DOI:
10.1371/journal.pntd.0010081.s001
DOI:
10.1371/journal.pntd.0010081.s002
DOI:
10.1371/journal.pntd.0010081.s003
DOI:
10.1371/journal.pntd.0010081.s004
DOI:
10.1371/journal.pntd.0010081.s005
DOI:
10.1371/journal.pntd.0010081.s006
DOI:
10.1371/journal.pntd.0010081.s007
DOI:
10.1371/journal.pntd.0010081.s008
DOI:
10.1371/journal.pntd.0010081.s009
DOI:
10.1371/journal.pntd.0010081.s010
DOI:
10.1371/journal.pntd.0010081.r001
DOI:
10.1371/journal.pntd.0010081.r002
DOI:
10.1371/journal.pntd.0010081.r003
DOI:
10.1371/journal.pntd.0010081.r004
DOI:
10.1371/journal.pntd.0010081.r005
DOI:
10.1371/journal.pntd.0010081.r006
Language:
English
Publisher:
Public Library of Science (PLoS)
Publication Date:
2022
detail.hit.zdb_id:
2429704-5
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