Eastern equine encephalitis virus rapidly infects and disseminates in the brain and spinal cord of cynomolgus macaques following aerosol challenge.

Autor: Williams JA; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Long SY; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Zeng X; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Kuehl K; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Babka AM; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Davis NM; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Liu J; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Trefry JC; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Daye S; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Facemire PR; Pathology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Iversen PL; Therapeutics Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Bavari S; Office of the Commander, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Pitt ML; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.; Office of the Commander, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America., Nasar F; Virology Division, United States Army Medical Research Institute of Infectious Diseases, Frederick, Maryland, United States of America.
Jazyk: angličtina
Zdroj: PLoS neglected tropical diseases [PLoS Negl Trop Dis] 2022 May 09; Vol. 16 (5), pp. e0010081. Date of Electronic Publication: 2022 May 09 (Print Publication: 2022).
DOI: 10.1371/journal.pntd.0010081
Abstrakt: 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.
Competing Interests: The authors have declared that no competing interests exist.
Databáze: MEDLINE
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