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

作者：Janice A. Williams, Simon Y. Long, Xiankun Zeng, Kathleen Kuehl, April M. Babka, Neil M. Davis, Jun Liu, John C. Trefry, Sharon P. Daye, Paul R. Facemire, Patrick L. Iversen, Sina Bavari, M. Louise M. Pitt, Farooq Nasar · 发表于：PLoS neglected tropical diseases · 年份：2022 · DOI：10.1371/journal.pntd.0010081 · 被引用次数：20 · 研究领域：Viral Infections and Vectors、Mosquito-borne diseases and control、Vector-Borne Animal Diseases

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 ...