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Cited by 157Mosquito-borne diseases and controlInfectious Encephalopathies and EncephalitisViral Infections and Vectors

Neurological sequelae resulting from encephalitic alphavirus infection

Open access
Ronca, Shannon E., Dineley, Kelly T., Paessler, Slobodan·2016·Frontiers in Microbiology
DOI 10.3389/fmicb.2016.00959PMC PMC4913092
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Abstract

The recent surge in viral clinical cases and associated neurological deficits have reminded us that viral infections can lead to detrimental, long-term effects, termed sequelae, in survivors. Alphaviruses are enveloped, single-stranded positive-sense RNA viruses in the Togaviridae family. Transmission of alphaviruses between and within species occurs mainly via the bite of an infected mosquito bite, giving alphaviruses a place among arboviruses, or arthropod-borne viruses. Alphaviruses are found throughout the world and typically cause arthralgic or encephalitic disease in infected humans. Originally detected in the 1930s, today the major encephalitic viruses include Venezuelan, Western, and Eastern equine encephalitis viruses (VEEV, WEEV, and EEEV, respectively). VEEV, WEEV, and EEEV are endemic to the Americas and are important human pathogens, leading to thousands of human infections each year. Despite awareness of these viruses for nearly 100 years, we possess little mechanistic understanding regarding the complications (sequelae) that emerge after resolution of acute infection. Neurological sequelae are those complications involving damage to the central nervous system that results in cognitive, sensory, or motor deficits that may also manifest as emotional instability and seizures in the most severe cases. This article serves to provide an overview of clinical cases documented in the past century as well as a summary of the reported neurological sequelae due to VEEV, WEEV, and EEEV infection. We conclude with a treatise on the utility of, and practical considerations for animal models applied to the problem of neurological sequelae of viral encephalopathies in order to decipher mechanisms and interventional strategies.

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Crossref · 10.3389/fmicb.2016.00959

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  • VEEV infections can have an adverse effect on learning memory.

    “Previous studies demonstrate that in animal models of neurodegenerative disorders, such as AD, cognitive function and learning and memory are significantly impaired (Anagnostaras et al., 2010; Chaudry et al., 2022; Kajs et al., 2022; Webster et al., 2014) and that VEEV infections can have an adverse effect on learning memory (Dave and Klein, 2023; Ronca et al., 2016).”

    From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Ronca et al., 2016

    The Clinical Cases section reports long-term neurological sequelae and neuropsychological changes after VEEV infection. The Summary of Sequelae mentions learning disabilities among alphavirus sequelae, but the paper’s explicit report of memory and learning deficits concerns Japanese encephalitis virus, not VEEV. It therefore supports adverse cognitive effects of VEEV without specifically establishing an effect on learning and memory. (LLM, conf=0.82)

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  • VEEV is a mosquito-borne alphavirus that causes a highly virulent central nervous system disease in horses and other equines with spill-over infections in humans.

    “Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that causes a highly virulent central nervous system (CNS) disease in horses and other equines with spill-over infections in humans [3,4].”

    From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [4]

    The Introduction identifies VEEV as a mosquito-transmitted encephalitic alphavirus, and Clinical Cases > Venezuelan Equine Encephalitis reports its isolation in equines and subsequent human disease. Neither passage establishes that VEEV causes a highly virulent CNS disease in horses or other equines, or characterizes human infections as spillover. Page numbers are not available in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • VEEV neurological sequelae share progressive characteristics of neurodegenerative disorders including cognitive, motor, or sensory deficits.

    “Although previous studies do not indicate VEEV is related to neurodegeneration, VEEV neurological sequelae share progressive characteristics of neurodegenerative disorders including cognitive, motor, or sensory deficits [4,14,15].”

    From VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice (2024) · cites this paper as [4]

    The Clinical Cases section defines neurological sequelae as including cognitive, sensory, and motor deficits and documents long-lasting sequelae after VEEV infection. It does not describe those deficits as progressive or compare them with neurodegenerative disorders. Page numbers are unavailable in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • New World alphaviruses such as Venezuelan equine encephalitis, eastern equine encephalitis, and western equine encephalitis viruses result in up to 90% of survivors exhibiting encephalitis and neurological sequelae.

    “New-world alphaviruses, such as Venezuelan equine encephalitis (VEE), eastern equine encephalitis (EEE), and western equine encephalitis (WEE) viruses, are spread within the Americas and result in up to 90% of survivors exhibiting encephalitis and neurological sequelae (Mulder et al., 1951; Rivas et al., 1997; Ronca et al., 2016)”

    From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Ronca et al., 2016

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2 of the 96 references couldn’t be matched to a known paper.

Research works printed but not linked: 1

  1. Griffin D. E. (2007). “ Alphaviruses,” in Fields Virology eds Knipe D. L. Howley P. M. Griffin D. E. Lamb R. A. Martin M. A. Roizman B. (Philadelphia, PA: Lippincott Williams & Wilkins), 1001– 1067.

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Authors
Ronca, S. E., Dineley, K. T., & Paessler, S.
Affiliations
The University of Texas Medical Branch at Galveston (US)
Corresponding author
Paessler, Slobodan
ORCID
Venue
Frontiers in Microbiology
Publisher
Frontiers Media SA
Published
2016-06-20
Volume
7
Pages
959-959
ISSN
1664-302X (ISSN-L)
DOI
10.3389/fmicb.2016.00959
PMC
PMC4913092
OpenAlex
W2439758191
Cited by
157
References
96
Citations by year
2026: 21 · 2025: 20 · 2024: 22 · 2023: 18 · 2022: 16 · 2021: 20 · 2020: 16 · 2019: 9 · 2018: 6 · 2017: 8
FWCI
1.15
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Microbiology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (TL1TR001440)
  • National Center for Advancing Translational Sciences
Topics
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
  • Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
  • Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
Keywords
alphavirus, neurological sequelae, encephalitis, Venezuelan equine encephalitis virus, western equine encephalitis virus, eastern equine encephalitis virus, arboviruses, mosquito-borne viral disease, Togaviridae

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