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• W3114730041 abstract "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. Following challenge, all parameters were rapidly and profoundly altered, and all nonhuman primates (NHPs) met the euthanasia criteria. In this study, we performed the first comprehensive pathology investigation of 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 of EEEV clinical disease course and pathogenesis in a NHP model and will provide significant insights into the evaluation of countermeasure. Author Summary EEEV is an arbovirus endemic in parts of North America and is able to produce fatal encephalitis in humans and domesticated animals. Despite multiple human outbreaks during the last 80 years, there are still no therapeutic or vaccines to treat or prevent human disease. One critical obstacle in the development of effective countermeasure is the lack of insights into EEEV pathogenesis in a susceptible animal host. We recently conducted a study in cynomolgus macaques to investigate the disease course by measuring clinical parameters relevant to humans. Following infection, these parameters were rapidly and profoundly altered leading to severe disease. In this study, we examined the potential mechanisms that underlie pathogenesis to cause severe disease. The virus was present in many parts of the brain and spinal cord, however, little or no pathological lesions as well as active virus replication were observed. Additionally, neurons were the predominant target of EEEV and virus transport was facilitated by axonal transport system to spread neuron-to-neuron throughout the brain and spinal cord. These data show that EEEV likely hijacks host cell transport system to rapidly spread in the brain and local/global neuronal dysfunction rather than death is the principal cause of severe disease." @default.
• W3114730041 created "2021-01-05" @default.
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• W3114730041 date "2020-12-21" @default.
• W3114730041 modified "2023-09-27" @default.
• W3114730041 title "Eastern Equine Encephalitis Virus Rapidly Infects and Disseminates in the Brain and Spinal Cord of Infected Cynomolgus Macaques Following Aerosol Challenge" @default.
• W3114730041 cites W1539578681 @default.
• W3114730041 cites W1853438253 @default.
• W3114730041 cites W1895905178 @default.
• W3114730041 cites W1963859054 @default.
• W3114730041 cites W1963905014 @default.
• W3114730041 cites W1967632255 @default.
• W3114730041 cites W1968077197 @default.
• W3114730041 cites W1971450473 @default.
• W3114730041 cites W1971726382 @default.
• W3114730041 cites W1976230117 @default.
• W3114730041 cites W1979712242 @default.
• W3114730041 cites W1980560678 @default.
• W3114730041 cites W1986539741 @default.
• W3114730041 cites W1997907373 @default.
• W3114730041 cites W1999721578 @default.
• W3114730041 cites W2011749173 @default.
• W3114730041 cites W2013704383 @default.
• W3114730041 cites W2016937865 @default.
• W3114730041 cites W2018944005 @default.
• W3114730041 cites W2022774983 @default.
• W3114730041 cites W2026225729 @default.
• W3114730041 cites W2027672450 @default.
• W3114730041 cites W2033783299 @default.
• W3114730041 cites W2038008568 @default.
• W3114730041 cites W2039371132 @default.
• W3114730041 cites W2039919932 @default.
• W3114730041 cites W2048470853 @default.
• W3114730041 cites W2058966115 @default.
• W3114730041 cites W2061817972 @default.
• W3114730041 cites W2066304777 @default.
• W3114730041 cites W2075871814 @default.
• W3114730041 cites W2082438000 @default.
• W3114730041 cites W2086420428 @default.
• W3114730041 cites W2086823430 @default.
• W3114730041 cites W2094365861 @default.
• W3114730041 cites W2101870877 @default.
• W3114730041 cites W2103779348 @default.
• W3114730041 cites W2108351400 @default.
• W3114730041 cites W2114282096 @default.
• W3114730041 cites W2119215990 @default.
• W3114730041 cites W2125343274 @default.
• W3114730041 cites W2126087307 @default.
• W3114730041 cites W2127513032 @default.
• W3114730041 cites W2132496473 @default.
• W3114730041 cites W2141344764 @default.
• W3114730041 cites W2143845740 @default.
• W3114730041 cites W2152143846 @default.
• W3114730041 cites W2155067706 @default.
• W3114730041 cites W2157510123 @default.
• W3114730041 cites W2159356412 @default.
• W3114730041 cites W2162754759 @default.
• W3114730041 cites W2164328155 @default.
• W3114730041 cites W2165634580 @default.
• W3114730041 cites W2168783824 @default.
• W3114730041 cites W2228656729 @default.
• W3114730041 cites W2325712009 @default.
• W3114730041 cites W2326710296 @default.
• W3114730041 cites W2329648226 @default.
• W3114730041 cites W2332004205 @default.
• W3114730041 cites W2336766681 @default.
• W3114730041 cites W2340031222 @default.
• W3114730041 cites W2347036201 @default.
• W3114730041 cites W2370564395 @default.
• W3114730041 cites W2470137146 @default.
• W3114730041 cites W2560908995 @default.
• W3114730041 cites W2587008617 @default.
• W3114730041 cites W2588086218 @default.
• W3114730041 cites W2646263679 @default.
• W3114730041 cites W2769146099 @default.
• W3114730041 cites W2789535842 @default.
• W3114730041 cites W2793514054 @default.
• W3114730041 cites W2796279370 @default.
• W3114730041 cites W2801125708 @default.
• W3114730041 cites W2882999515 @default.
• W3114730041 cites W2883220758 @default.
• W3114730041 cites W2899206050 @default.
• W3114730041 cites W2900372023 @default.
• W3114730041 cites W2904615123 @default.
• W3114730041 cites W2913494007 @default.
• W3114730041 cites W2945709598 @default.
• W3114730041 cites W3008947151 @default.

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