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A Murine Model of Dengue Virus-induced Acute Viral Encephalitis-like Disease
Published on: April 28, 2019
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Physiological and immunological changes in the brain associated with lethal eastern equine encephalitis virus in
Joseph R Albe1, Henry Ma1,2, Theron H Gilliland1
1Center for Vaccine Research, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America.
Plos Pathogens
|February 3, 2021
Summary
Eastern equine encephalitis virus (EEEV) causes lethal encephalitis in macaques. Monitoring brain activity and pressure may help evaluate EEEV treatments.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Eastern equine encephalitis virus (EEEV) causes severe human encephalitis.
- Cynomolgus macaques exposed to EEEV via aerosol develop a lethal disease mimicking human outcomes.
- Understanding EEEV pathophysiology in macaques is crucial for developing medical countermeasures under the Animal Rule.
Purpose of the Study:
- To investigate the pathophysiology of EEEV encephalitis in cynomolgus macaques.
- To identify biomarkers for central nervous system (CNS) infection and disease outcome.
- To evaluate novel physiological monitoring methods for assessing therapeutic efficacy.
Main Methods:
- Lethal dose of EEEV strain V105 administered via aerosol to cynomolgus macaques.
- Monitoring of fever, viremia, electroencephalography (EEG), and intracranial pressure (ICP).
- Analysis of plasma biomarkers (IP-10), leukocyte infiltration, gene expression in brain tissue, and viral load at necropsy.
Main Results:
- Macaques developed fever, increased delta EEG power, and elevated ICP, succumbing by 6 days post-infection.
- Early infection showed granulocytosis, elevated IP-10, and peak viremia before fever onset.
- Brain tissues exhibited increased expression of traumatic brain injury genes and inflammatory cytokines; lymphoid cells predominated leukocyte infiltration.
Conclusions:
- EEEV encephalitis in macaques involves overwhelming CNS viral infection and a significant inflammatory response.
- EEG and ICP monitoring show promise as novel methods for evaluating EEEV therapeutics in this model.
- Biomarkers like IP-10 and gene expression changes aid in understanding disease progression and evaluating countermeasures.
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