Immunopathogenesis and immune modulation of Venezuelan equine encephalitis virus-induced disease in the mouse
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The course of Venezuelan equine encephalitis (VEE) disease in immunodeficient and immunologically normal mice was compared to define the role of the immune system in this disease process. Immunocompetent mice infected with VEE exhibited a biphasic illness characterized by an early self-limiting lymphoid phase and a fatal CNS phase. The lymphoid phase of the illness was characterized by extensive viral replication within spleen, thymus, Peyer's patches, and lymph nodes, was accompanied by a high-titered serum viremia, and resolved with the production of VEE-specific IgM class antibody at 72 h postinfection (p.i.). Immunocompetent animals survived an average of 6.8 +/- 1.2 days before succumbing to fulminant encephalitis. In contrast, SCID mice infected with VEE showed a persistent replication of virus throughout all organs tested beginning at 24 h p.i. VEE-infected SCID mice exhibited a severe spongiform encephalopathy with 100% mortality and an average survival time of 8.9 +/- 0.9 days. These studies indicated that the characteristic organ tropism of VEE in the mouse is due in large part to an early anti-viral state, the establishment of which is dependent upon the presence of an intact immune system. Finally, the CNS pathology in a VEE-infected mouse had a significant immunologic component. However, in contrast to other neurovirulent alphaviruses, VEE was directly cytopathic for the cells of the CNS, even in the absence of an immune response.
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VEEV infection induces neuropathology, including meningoencephalitis, gliosis, and multifocal neuropil vacuolation, localized to multiple regions including the hippocampus.
“It induces neuropathology, including meningoencephalitis, gliosis, and multifocal neuropil vacuolation, which is localized to multiple regions, including the hippocampus (Charles et al., 2001; Kundin et al., 1966; Schoneboom et al., 2000; A. Taylor et al., 2015).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Charles et al., 2001
The CNS histopathology section reports leptomeningitis and inflammatory infiltration in VEE-infected immunocompetent mice, but spongiosis with microglial and astrocytic proliferation in SCID mice. The CNS pathogenesis section also reports neuropil vacuolation in SCID mice. The paper says spongiosis was widely distributed throughout the CNS, but the passages do not specifically locate lesions in the hippocampus; the sentence also combines findings from mice with different immune status. (LLM, conf=0.88)
Experimental — accuracy not yet measuredVEEV infection characteristically induces an intense inflammatory response, initiating perivascular and interstitial mononuclear infiltrate in the brain.
“VEEV infection characteristically induces an intense inflammatory response, initiating perivascular and interstitial mononuclear infiltrate in the brain.”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Charles et al., 2001
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References 45 · Cited by 79
Research works printed but not linked: 3
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- Authors
- Charles, P. C., Trgovcich, J., Davis, N. L., & Johnston, R. E.
- Affiliations
- University of North Carolina at Chapel Hill (US)
- Corresponding author
- Charles, Peter C.
- Venue
- Virology
- Publisher
- Elsevier BV
- Published
- 2001-06
- Volume
- 284
- Issue
- 2
- Pages
- 190-202
- ISSN
- 0042-6822 (ISSN-L)
- OpenAlex
- W2062915219
- Cited by
- 79
- References
- 45
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 3 · 2023: 3 · 2022: 4 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 3 · 2017: 2 · 2016: 3 · 2015: 3 · 2014: 4 · 2013: 3 · 2012: 3
- FWCI
- 1.16
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Virology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Science Foundation
- National Institutes of Health (5r01ns026681-09)
- National Institute of Allergy and Infectious Diseases (T32AI07419, AI22186, R01AI022186, T32AI007419)
- National Institute of Neurological Disorders and Stroke (NS26681)
- Army Research Office
- U.S. Army Medical Research and Development Command
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
- Health Sciences › Medicine › Epidemiology › Virology and Viral Diseases
- Keywords
- Venezuelan equine encephalitis virus, immunopathogenesis, immunomodulation, SCID mice, immunodeficient mice, spongiform encephalopathy, viremia, IgM antibody response, cytopathic effect, organ tropism
- MeSH terms
- Animals, Antibodies, Viral, Brain, Disease Models, Animal, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Female, Immunoglobulin M, Lymph Nodes, Mice, Inbred BALB C, Necrosis, Neurons, Peyer's Patches, Spleen, Thymus Gland, Time Factors, Viremia, Mice, SCID, Mice
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