ArticlePLoS pathogens2021
Physiological and immunological changes in the brain associated with lethal eastern equine encephalitis virus in macaques.
Article in PLoS pathogens, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 27 citations in OpenAlex.
- Arboviral infections of the central nervous system: Mechanisms of invasion and long-term consequences.Journal of neurovirology · 2026Review
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- Hidden in Plain Sight: Alphavirus Persistence and Its Potential for Driving Chronic Pathogenesis.Viruses · 2025Review
- Chronic Neuroplasticity Changes Following Neurotropic Viral Infection: Mechanisms and Implications.Cellular and molecular neurobiology · 2025Review
- An inactivated trivalent virion-based vaccine protects against aerosol challenge with encephalitic alphaviruses in mice and macaques.Science translational medicine · 2025Article
- Three positively charged binding sites on the eastern equine encephalitis virus E2 glycoprotein coordinate heparan sulfate- and protein receptor-dependent infection.Nature communications · 2025Article
- Modeling Virus-Associated Central Nervous System Disease in Non-Human Primates.International journal of molecular sciences · 2025Review
- A detailed kinetic model of Eastern equine encephalitis virus replication in a susceptible host cell.PLoS computational biology · 2025Article
- Successful Inactivation of High-Consequence Pathogens in PrimeStore Molecular Transport Media.Viruses · 2025Article
- Neuropathogenesis of Encephalitic Alphaviruses in Non-Human Primate and Mouse Models of Infection.Pathogens (Basel, Switzerland) · 2025Review
- SIV-specific antibodies protect against inflammasome-driven encephalitis in untreated macaques.Cell reports · 2024Article
- Cytomegalovirus vaccine vector-induced effector memory CD4 + T cells protect cynomolgus macaques from lethal aerosolized heterologous avian influenza challenge.Nature communications · 2024Article
- MVA-based vaccines are protective against lethal eastern equine encephalitis virus aerosol challenge in cynomolgus macaques.NPJ vaccines · 2024Article
- Neurological manifestations of encephalitic alphaviruses, traumatic brain injuries, and organophosphorus nerve agent exposure.Frontiers in neuroscience · 2024Review
- Refined semi-lethal aerosol H5N1 influenza model in cynomolgus macaques for evaluation of medical countermeasures.iScience · 2023Article
- Bunyavirales: Scientific Gaps and Prototype Pathogens for a Large and Diverse Group of Zoonotic Viruses.The Journal of infectious diseases · 2023Article
- Developing a Prototype Pathogen Plan and Research Priorities for the Alphaviruses.The Journal of infectious diseases · 2023Article
- Eastern Equine Encephalitis Virus Diversity in Massachusetts Patients, 1938-2020.The American journal of tropical medicine and hygiene · 2023Article
- Efficacy of a brain-penetrant antiviral in lethal Venezuelan and eastern equine encephalitis mouse models.Science translational medicine · 2023Article
Corrections and comments
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Aerosol exposure to eastern equine encephalitis virus (EEEV) can trigger a lethal viral encephalitis in cynomolgus macaques which resembles severe human disease. Biomarkers indicative of central nervous system (CNS) infection by the virus and lethal outcome of disease would be useful in evaluating potential medical countermeasures, especially for therapeutic compounds. To meet requirements of the Animal Rule, a better understanding of the pathophysiology of EEEV-mediated disease in cynomolgus macaques is needed. In this study, macaques given a lethal dose of clone-derived EEEV strain V105 developed a fever between 2-3 days post infection (dpi) and succumbed to the disease by 6 dpi. At the peak of the febrile phase, there was a significant increase in the delta electroencephalography (EEG) power band associated with deep sleep as well as a sharp rise in intracranial pressure (ICP). Viremia peaked early after infection and was largely absent by the onset of fever. Granulocytosis and elevated plasma levels of IP-10 were found early after infection. At necropsy, there was a one hundred- to one thousand-fold increase in expression of traumatic brain injury genes (LIF, MMP-9) as well as inflammatory cytokines and chemokines (IFN-γ, IP-10, MCP-1, IL-8, IL-6) in the brain tissues. Phenotypic analysis of leukocytes entering the brain identified cells as primarily lymphoid (T, B, NK cells) with lower levels of infiltrating macrophages and activated microglia. Massive amounts of infectious virus were found in the brains of lethally-infected macaques. While no infectious virus was found in surviving macaques, quantitative PCR did find evidence of viral genomes in the brains of several survivors. These data are consistent with an overwhelming viral infection in the CNS coupled with a tremendous inflammatory response to the infection that may contribute to the disease outcome. Physiological monitoring of EEG and ICP represent novel methods for assessing efficacy of vaccines or therapeutics in the cynomolgus macaque model of EEEV encephalitis.
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