Inflammation is a component of neurodegeneration in response to Venezuelan equine encephalitis virus infection in mice
Abstract
Infection with the mosquito-transmitted Venezuelan equine encephalitis virus (VEE) causes an acute systemic febrile illness followed by meningoencephalitis. In this communication we characterize the cytokine profile induced in the central nervous system (CNS) in response to virulent or attenuated strains of VEE using RNase Protection Assays. Virulent VEE causes an upregulation of multiple pro-inflammatory genes including inducible nitric oxide synthase (iNOS) and tumor necrosis factor alpha (TNF-alpha). To determine if iNOS and TNF-alpha contribute to the neuropathogenesis of VEE infection, iNOS and TNF receptor knockout mice were used in VEE mortality studies and exhibited extended survival times. Finally, CNS tissue sections labeled for VEE antigen, and adjacent sections double-labeled for an astrocyte marker and apoptosis, revealed that apoptosis of neurons occurs not only in areas of the brain positive for VEE-antigen, but also in areas of astrogliosis. These findings suggest that the inflammatory response, which is in part mediated by iNOS and TNF-alpha, may contribute to neurodegeneration following encephalitic virus infection.
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VEEV infection causes gliosis and neuroinflammation, indicating indirect mechanisms of neuronal degeneration, like neurotoxic mechanisms related to Alzheimer's disease.
“VEEV infection causes gliosis and neuroinflammation, indicating indirect mechanisms of neuronal degeneration, like neurotoxic mechanisms related to AD (Schoneboom et al., 2000).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Schoneboom et al., 2000
VEEV infects neurons and glial cells in the CNS, promoting neurodegeneration and potentially leading to permanent neurological sequelae during its lymphotropic and neurotropic phases.
“It infects neurons and glial cells in the CNS, promoting neurodegeneration and potentially leading to permanent neurological sequelae during its lymphotropic and neurotropic phases (Bocan et al., 2019; Gleiser et al., 1962; Schoneboom et al., 2000).”
From Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model (2024) · cites this paper as Schoneboom et al., 2000
VEEV 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 Schoneboom et al., 2000
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 Schoneboom et al., 2000
Cites
Astrocytes as targets for Venezuelan equine encephalitis virus infection
Schoneboom, B. A., Fultz, M. J., Miller, T. H., McKinney, L. C., & Grieder, F. B. (1999) · Journal of Neurovirology · doi:10.3109/13550289909029475 · Cited by 58 · cited 5× · see citing works
“Materials and methods ly described (McCarthy and de Vellis, 1980; Schoneboom et al., 1999).”
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V <scp>ENEZUELAN</scp> E <scp>QUINE</scp> E <scp>NCEPHALITIS</scp>
Weaver, S. C., Ferro, C., Barrera, R., Boshell, J., & Navarro, J.-C. (2004) · Annual Review of Entomology · doi:10.1146/annurev.ento.49.061802.123422 · Cited by 465 · see citing works
Inflammatory Neurodegeneration Mediated by Nitric Oxide, Glutamate, and Mitochondria
Brown, G. C., & Bal‐Price, A. (2003) · Molecular Neurobiology · doi:10.1385/mn:27:3:325 · Cited by 461 · see citing works
Regulation of Inducible Nitric Oxide Synthase Gene in Glial Cells
Saha, R. N., & Pahan, K. (2006) · Antioxidants and Redox Signaling · doi:10.1089/ars.2006.8.929 · Cited by 353 · see citing works
Steele, K., & Twenhafel, N. (2010) · Veterinary Pathology · doi:10.1177/0300985810372508 · Cited by 314 · see citing works
“One study attributed neuronal damage in parts of the brain without apparent VEEV infection to activation of astrocytes.(77) The same study also reported upregulation of a variety of apoptosis-signaling molecules in the brains of infected mice, although the cellular source of these mediators was not determined.”
BackgroundTheiler's Virus Infection: a Model for Multiple Sclerosis
Oleszak, E. L., Chang, J. R., Friedman, H. P., Katsetos, C. D., & Platsoucas, C. D. (2004) · Clinical Microbiology Reviews · doi:10.1128/cmr.17.1.174-207.2004 · Cited by 307 · see citing works
Viral diseases of the central nervous system
Swanson, P. A., & McGavern, D. B. (2015) · Current Opinion in Virology · doi:10.1016/j.coviro.2014.12.009 · Cited by 314 · see citing works
Chikungunya fever: CNS infection and pathologies of a re-emerging arbovirus.
Das, T., Jaffar-Bandjee, M., Hoarau, J., Krejbich-Trotot, P., Denizot, M., Lee-Pat-Yuen, G., Sahoo, R., Guiraud, P., Ramful, D., Robin, S., et al. (2010) · Progress in neurobiology · doi:10.1016/j.pneurobio.2009.12.006 · Cited by 204 · see citing works
Apoptosis in animal models of virus-induced disease
Clarke, P., & Tyler, K. (2009) · Nature Reviews Microbiology · doi:10.1038/nrmicro2071 · Cited by 184 · see citing works
“gov/sites/entrez?Db=genome&Cmd=ShowDetailView&TermToSearch=10176">VEE ) or the rat CNS with Borna disease virus ( BDV ), apoptosis occurs in areas that lack viral antigen but do show evidence of astrogliosis and inflammation (in the case of VEE”
Host responses to alphavirus infection
Ryman, K. D., & Klimstra, W. B. (2008) · Immunological Reviews · doi:10.1111/j.1600-065x.2008.00670.x · Cited by 169 · see citing works
“Furthermore, VEEV (78) and SFV (127) can infect glial cells in vitro, and models in which the capacity of glial cell activation and inflammatory mediator release is limited exhibit reduced disease manifestations after infection with neurovirulent alphaviruses (77, 79).”
BackgroundViral (aseptic) meningitis: A review.
Wright, W. F., Pinto, C. N., Palisoc, K., & Baghli, S. (2019) · Journal of the Neurological Sciences · doi:10.1016/j.jns.2019.01.050 · Cited by 116 · see citing works
Vaccines for Venezuelan equine encephalitis
Paessler, S., & Weaver, S. C. (2009) · Vaccine · doi:10.1016/j.vaccine.2009.07.095 · Cited by 114 · see citing works
“Previous studies have demonstrated that the murine model is characterized by biphasic disease, which starts with the productive infection of lymphoid tissue and culminates in the destruction of the CNS by viral replication and a “toxic” neuroinflammatory response that is uniformly lethal [10–16].”
Viral Encephalitis and Neurologic Diseases: Focus on Astrocytes
Soung, A., & Klein, R. S. (2018) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2018.09.001 · Cited by 116 · see citing works
“Similarly, alphaviruses can indirectly cause neuronal death via the release of proinflammatory cytokines and enhanced neurotoxicity [7].”
BackgroundEncephalitic Arboviruses: Emergence, Clinical Presentation, and Neuropathogenesis
Salimi, H., Cain, M. D., & Klein, R. (2016) · Neurotherapeutics · doi:10.1007/s13311-016-0443-5 · Cited by 108 · see citing works
“istic of apoptosis, that is, nuclear andmembrane condensation, after infection with several encephalitic flaviviruses, including WNV [183], JEV [154], TBEV [184], and alphaviruses [145, 185, 186].”
BackgroundCentral nervous system apoptosis in human herpes simplex virus and cytomegalovirus encephalitis.
DeBiasi, R., Kleinschmidt-DeMasters, B., Richardson-Burns, S., & Tyler, K. (2002) · Journal of Infectious Diseases · doi:10.1086/345375 · Cited by 95 · see citing works
Sharma, A., & Knollmann-Ritschel, B. (2019) · Viruses · doi:10.3390/v11020164 · Cited by 88 · see citing works
“Encephalitis in VEEV is associated with the up-regulation of multiple inflammatory mediators such as toll-like receptor signaling, cytokine-inducible nitric oxide synthase (iNOS), tumor necrosis factors alpha (TNF-α), transforming growth factor-beta (TGF-β), interleukins and chemokines [14,37,38,40,109].”
BackgroundInfluentialJaffar-Bandjee, M., Das, T., Hoarau, J., Krejbich-Trotot, P., Denizot, M., Ribéra, A., Roques, P., & Gasque, P. (2009) · Microbes and infection · doi:10.1016/j.micinf.2009.10.001 · Cited by 86 · see citing works
Paessler, S., Ni, H.-L., Petrakova, O., Fayzulin, R. Z., Yun, N., Anishchenko, M., Weaver, S., & Frolov, I. (2006) · Journal of Virology · doi:10.1128/jvi.80.6.2784-2796.2006 · Cited by 82 · see citing works
“By the time encephalitis has developed in an infected mouse, the infectious virus is usually absent from the peripheral organs and blood (12, 13, 15, 16, 39, 42, 43).”
BackgroundSharma, A., Bhattacharya, B., Puri, R., & Maheshwari, R. (2008) · BMC Genomics · doi:10.1186/1471-2164-9-289 · Cited by 62 · see citing works
“Activated glial cells are observed in the brains of VEEV-infected mice [10, 11 ].”
BackgroundInfluentialSchoneboom, B., Lee, J. S., & Grieder, F. B. (2000) · Journal of Interferon and Cytokine Research · doi:10.1089/107999000312621 · Cited by 59 · see citing works
Self-citationJulander, J., Skirpstunas, R., Siddharthan, V., Shafer, K., Hoopes, J. D., Smee, D., & Morrey, J. (2008) · Antiviral Research · doi:10.1016/j.antiviral.2008.01.007 · Cited by 58 · see citing works
“, 1991; Jordan, 1973), cytokine induction (Grieder et al., 1997; Schoneboom et al., 2000), relative resistance (treatment was effective only at concentrations of 106.”
BackgroundResultInfluentialBaer, A., Lundberg, L., Swales, D. A., Waybright, N., Pinkham, C., Dinman, J. D., Jacobs, J. L., & Kehn‐Hall, K. (2016) · Journal of Virology · doi:10.1128/jvi.02827-15 · Cited by 64 · see citing works
“Specifically, numerous proinflammatory cytokines, including interleu-kin-1 (IL-1), IL-6, IL-12, glycogen synthase kinase 3, inducible nitric oxide synthase, and tumor necrosis factor alpha (TNF-␣), have all been shown to play a role in VEEV pathogenesis (49) (50) (51) (52) (53) .”
BackgroundModulation of GSK-3β Activity in Venezuelan Equine Encephalitis Virus Infection
Kehn‐Hall, K., Narayanan, A., Lundberg, L., Sampey, G. C., Pinkham, C., Guendel, I., Duyne, R. V., Senina, S., Schultz, K. L. W., Stavale, E. J., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0034761 · Cited by 52 · see citing works
“Non-infected neurons are also subject to bystander affects, as no VEEV antigen could be found in a subset of dying neurons [48,50].”
BackgroundKosmac, K., Bantug, G., Pugel, E., Cekinović, D., Jonjić, S., & Britt, W. (2013) · PLoS Pathogens · doi:10.1371/journal.ppat.1003200 · Cited by 49 · see citing works
Sharma, A., & Maheshwari, R. (2009) · Journal of General Virology · doi:10.1099/vir.0.010280-0 · Cited by 46 · see citing works
“…against VEEV, but neurodegeneration following VEEV infection in the brain is also widely believed to be due to excessive inflammatory response to virus presence in the brain (Charles et al., 2001; Grieder & Vogel, 1999; Jackson et al., 1991; Schoneboom et al., 1999, 2000a, b; White et al., 2001).”
BackgroundImmunopathogenesis of alphaviruses
Baxter, V. K., & Heise, M. (2020) · Advances in Virus Research · doi:10.1016/bs.aivir.2020.06.002 · Cited by 45 · see citing works
Treatment of Venezuelan Equine Encephalitis Virus Infection with (-)-Carbodine
Julander, J., Bowen, R., Rao, J. R., Day, C., Shafer, K., Smee, D., Morrey, J., & Chu, C. K. (2008) · Antiviral Research · doi:10.1016/j.antiviral.2008.07.002 · Cited by 43
“In general, attenuated VEEV strains will replicate to high titers in the brain of different mouse strains, but there is usually no morbidity or mortality associated with infection (Ludwig et al., 2001; Schoneboom et al., 2000).”
BackgroundValero, N., Mosquera, J., Alcocer, S., Bonilla, E., Salazar, J., & Álvarez-Mon, M. (2015) · Brain Research · doi:10.1016/j.brainres.2015.06.034 · Cited by 42 · see citing works
Winkler, C. W., Woods, T. A., Groveman, B. R., Carmody, A., Speranza, E. E., Martens, C., Best, S. M., Haigh, C. L., & Peterson, K. E. (2019) · Journal of Neuroinflammation · doi:10.1186/s12974-019-1614-1 · Cited by 55 · see citing works
EGR1 Upregulation during Encephalitic Viral Infections Contributes to Inflammation and Cell Death
Lehman, C., Smith, A., Kelly, J. A., Jacobs, J. L., Dinman, J. D., & Kehn-Hall, K. (2022) · Viruses · doi:10.3390/v14061210 · Cited by 37 · see citing works
“TNF-α is upregulated following VEEV infection and studies involving TNF receptor knockout mice resulted in extended survival times [70].”
BackgroundAl-Obaidi, M. M. J., Bahadoran, A., Har, L. S., Mui, W. S., Rajarajeswaran, J., Zandi, K., Manikam, R., & Sekaran, S. (2017) · Virus Research · doi:10.1016/j.virusres.2017.02.012 · Cited by 34 · see citing works
“Fasl expression has been shown to be a good indicator for neuronal apoptosis following encephalitic arboviral infections such as tick-borne encephalitis and Venezuelan equine encephalitic viruses (Schoneboom et al., 2000; Sharma et al., 2008).”
BackgroundHu, W.-G., Phelps, A., Jager, S., Chau, D., Hu, C., O'Brien, L., Perkins, S. D., Gates, A., Phillpotts, R., & Nagata, L. (2010) · Vaccine · doi:10.1016/j.vaccine.2010.06.038 · Cited by 34 · see citing works
Small molecule inhibitors of Ago2 decrease Venezuelan equine encephalitis virus replication.
Madsen, C., Hooper, I., Lundberg, L., Shafagati, N., Johnson, A., Senina, S., de la Fuente, C. L., Hoover, L. I., Fredricksen, B. L., Dinman, J. D., et al. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.10.002 · Cited by 29
Bocan, T. M., Stafford, R. G., Brown, J. L., Akuoku Frimpong, J., Basuli, F., Hollidge, B. S., Zhang, X., Raju, N., Swenson, R. E., & Smith, D. R. (2019) · Viruses · doi:10.3390/v11111052 · Cited by 29 · see citing works
“VEEV TC-83 and other attenuated VEEV strains can replicate in the brains of many mouse strains without causing mortality [5,6].”
BackgroundSafieh‐Garabedian, B., Ochoa‐Chaar, C. I., Poole, S., Massaad, C. A., Atweh, S., Jabbur, S. J., & Saadé, N. E. (2003) · Neuroscience · doi:10.1016/s0306-4522(03)00500-1 · Cited by 29 · see citing works
Pineal hormone melatonin as an adjuvant treatment for COVID-19 (Review)
Vlachou, M., Siamidi, A., Dedeloudi, A., Konstantinidou, S., & Papanastasiou, I. P. (2021) · International Journal of Molecular Medicine · doi:10.3892/ijmm.2021.4880 · Cited by 27 · see citing works
Konopka, J. L., Thompson, J. M., Whitmore, A. C., Webb, D. L., & Johnston, R. E. (2009) · Journal of Virology · doi:10.1128/jvi.00564-09 · Cited by 25 · see citing works
A Two-Phase Innate Host Response to Alphavirus Infection Identified by mRNP-Tagging In Vivo
Konopka, J. L., Penalva, L. O., Thompson, J. M., White, L. J., Beard, C., Keene, J., & Johnston, R. (2007) · PLoS Pathogens · doi:10.1371/journal.ppat.0030199 · Cited by 25
“While alphavirus CNS pathogenesis has been studied extensively in several model systems, it has been suggested that multiple host- and virus-specific parameters contribute to VEE-induced pathology in the brain [50–52].”
BackgroundValero, N., MarinaEspina, L., Bonilla, E., & Mosquera, J. (2007) · Journal of Pineal Research · doi:10.1111/j.1600-079x.2006.00381.x · Cited by 25 · see citing works
“As, NO could be an important oxidant and apoptosis inducer in an autocrine and paracrine manners during VEE virus infection [2, 19], a beneficial effect of melatonin may be related to the capacity of the indole to reduce the levels of intracellular NO with further reduction of its extra cellular concentration.”
BackgroundHollidge, B. S., Cohen, C. A., Frimpong, J. A., Badger, C. V., Dye, J. M., & Schmaljohn, C. S. (2021) · Virulence · doi:10.1080/21505594.2020.1870834 · Cited by 28 · see citing works
“In addition, iNOS knockout mice infected with wild-type VEEV have increased survival times [39], but these mice are still susceptible to LPS-induced death [43].”
BackgroundMouse model of neurological complications resulting from encephalitic alphavirus infection
Ronca, S. E., Smith, J., Koma, T., Miller, M. M., Yun, N., Dineley, K. T., & Paessler, S. (2017) · Frontiers in Microbiology · doi:10.3389/fmicb.2017.00188 · Cited by 22 · see citing works
“This cytotoxicity in conjunction with infection of other CNS cell types leads to neuroinflammation (Schoneboom et al., 2000).”
BackgroundGupta, P., Sharma, A., Han, J., Yang, A. X., Bhomia, M., Knollmann-Ritschel, B., Puri, R., & Maheshwari, R. (2017) · BMC Infectious Diseases · doi:10.1186/s12879-017-2355-3 · Cited by 21 · see citing works
“Activation of inflammatory cells is critical to virus clearance however; and the excessive inflammation in the brain caused by VEEV has been implicated in neurodegeneration [6, 7, 9, 12].”
BackgroundNeuropathogenesis of Encephalitic Alphaviruses in Non-Human Primate and Mouse Models of Infection
Lehman, C. W., Carney, S. K., & Kehn‐Hall, K. (2025) · Pathogens · doi:10.3390/pathogens14020193 · Cited by 20 · see citing works
“The proinflammatory mediators nitric oxide synthase ( iNOS ) and TNF α were also upregulated in the brains of VEEV-infected mice [103].”
Direct and indirect pro-inflammatory cytokine response resulting from TC-83 infection of glial cells
Keck, F., Kortchak, S., Bakovic, A., Roberts, B., Agrawal, N., & Narayanan, A. (2018) · Virulence · doi:10.1080/21505594.2018.1509668 · Cited by 23 · see citing works
Analysis of microRNAs induced by Venezuelan equine encephalitis virus infection in mouse brain
Bhomia, M., Balakathiresan, N. S., Sharma, A. K., Gupta, P., Biswas, R., & Maheshwari, R. K. (2010) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2010.03.091 · Cited by 22 · see citing works
“Inflammation in CNS plays an important role in the disease outcome and is often believed to be associated with the secondary neuronal damage in brain [5–7].”
BackgroundKeck, F., Khan, D. H., Roberts, B., Agrawal, N., Bhalla, N., & Narayanan, A. (2018) · Viruses · doi:10.3390/v10110606 · Cited by 19 · see citing works
Peng, B., Borisevich, V., Popov, V. L., Zacks, M. A., Estes, D. M., Campbell, G. A., & Paessler, S. (2013) · Veterinary Microbiology · doi:10.1016/j.vetmic.2012.11.021 · Cited by 17 · see citing works
“While the neuronal cell population is the major target for VEEV infection, it is unclear to what degree astrocytes may be involved in amplifying the virus and/or orchestrating the inflammatory response (Schoneboom et al., 2000 (Schoneboom et al., , 1999 .”
BackgroundSteele, K., Seth, P., Catlin-Lebaron, K. M. K., Schoneboom, B., Husain, M. M., Grieder, F., & Maheshwari, R. K. (2006) · Veterinary Pathology-Supplement · doi:10.1354/vp.43-6-904 · Cited by 19
Self-citationValero, N., Espina, L. M., & Mosquera, J. (2006) · Neurochemical Research · doi:10.1007/s11064-006-9098-7 · Cited by 19
“Since, extra cellular NO could be an important oxidant and apoptosis inducer on other cells [3, 18], a beneficial effect of MTL could be related to the capacity of the hormone to reduce the amount of intracellular NO with further reduction of its extra cellular concentration.”
BackgroundRisner, K. H., Ahmed, A., Bakovic, A., Kortchak, S., Bhalla, N., & Narayanan, A. (2019) · Viruses · doi:10.3390/v11121151 · Cited by 18 · see citing works
“The highest mRNA inductions were observed for IL1A, IL17F, CCR4, CCR8, CX3CL1 and TNFα (Figure 5).”
BackgroundInfluentialConstantin, D., Ala'aldeen, D., & Murphy, S. (2002) · Journal of Neurochemistry · doi:10.1046/j.1471-4159.2002.00816.x · Cited by 17 · see citing works
Greenlee, J. (2014) · Handbook of Clinical Neurology · doi:10.1016/b978-0-444-53488-0.00019-5 · Cited by 15
Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses
Ogorek, T. J., & Golden, J. E. (2023) · Viruses · doi:10.3390/v15020413 · Cited by 13 · see citing works
Lundberg, L., Fontenot, J., Lin, S.-C., Pinkham, C., Carey, B., Campbell, C., & Kehn-Hall, K. (2018) · Frontiers in Microbiology · doi:10.3389/fmicb.2018.03126 · Cited by 13 · see citing works
“Astrogliosis as indicated by increased GFAP staining, a marker of astrocyte proliferation, and apoptosis were observed in VEEV infected mice (Schoneboom et al., 2000).”
BackgroundPhelps, A. L., Salguero, F. J., Hunter, L. E., Stoll, A. L., Jenner, D. C., O’Brien, L. M., Williamson, E. D., Lever, M. S., & Laws, T. R. (2023) · Viruses · doi:10.3390/v15061307 · Cited by 13 · see citing works
“Moreover, targeting TNF-α pharmacologically may have similar effects to those observed in knockout mice [33,34].”
BackgroundLee, J., Parvathareddy, J., Yang, D., Bansal, S., O’Connell, K., Golden, J. E., & Jonsson, C. (2020) · Journal of Virology · doi:10.1128/jvi.00317-20 · Cited by 11 · see citing works
“VEEV has been shown to replicate in astroglia in the central nervous system (22, 23).”
BackgroundFongsaran, C., Jirakanwisal, K., Peng, B.-H., Fracassi, A., Taglialatela, G., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Brain, Behavior, & Immunity - Health · doi:10.1016/j.bbih.2024.100780 · Cited by 9 · see citing works
“South and Central American outbreaks of VEEV produce a highly virulent central nervous system (CNS) disease in horses and other equines (Schoneboom et al., 2000).”
BackgroundInfluentialThe Host Non-Coding RNA Response to Alphavirus Infection
Behnia, M., & Bradfute, S. B. (2023) · Viruses · doi:10.3390/v15020562 · Cited by 9 · see citing works
“The elevated expression of proinflammatory cytokines, including IL-1β, has been reported in the brains of VEEV-infected mice, which results in increased inflammation leading to neuronal cell death and brain damage [72,73].”
BackgroundVirus signaling and apoptosis in the central nervous system infection.
Perkins, D. (2005) · Frontiers in Bioscience · doi:10.2741/1737 · Cited by 8
CHAPTER 20 – Equine Alphaviruses
Long, M., & Gibbs, E. (2007) · doi:10.1016/b978-1-4160-2406-4.50025-9 · Cited by 8
Rangel, M. V., Sebastian, A., Leon, N. F., Phillips, A. M., Gorman, B. M., Hum, N. R., & Weilhammer, D. R. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1497839 · Cited by 7 · see citing works
Williams, E. P., Xue, Y., Vogel, P., Yang, D., Ponce-Flores, A., Li, X.-Y., Ogorek, T. J., Saini, M., Iulek, J., Ruiz, F., et al. (2025) · Journal of Virology · doi:10.1128/jvi.01679-24 · Cited by 6 · see citing works
Long-lasting astrocyte reaction to persistent Junin virus infection of rat cortical neurons
Caccuri, R. L., Iacono, R., Weissenbacher, M. C., Ávila, M., & Berría, M. (2003) · Journal of neural transmission · doi:10.1007/s00702-003-0010-1 · Cited by 6
The fine line between protection and pathology in neurotropic flavivirus and alphavirus infections
Ong, R.-Y., Lum, F., & Ng, L. (2014) · Future Virology · doi:10.2217/fvl.14.6 · Cited by 4 · see citing works
Role of angiotensin II in experimental Venezuelan equine encephalitis in rats
Bermúdez, J., Valero, N., Mosquera, J., Vargas, R., Hernandez-Fonseca, J. P., Quiroz, Y., & Godoy, R. (2015) · Archives of Virology · doi:10.1007/s00705-015-2521-0 · Cited by 3 · see citing works
“This infection has been shown to result in perivascular cuffing with infiltrating lymphocytes, gliosis, activation of glial cells, cerebral edema, neurodegeneration, and apoptosis associated with astrogliosis [4, 5].”
BackgroundWilliams, E. P., Xue, Y., Yang, D., Lee, J., Kim, E., Ponce-Flores, A., Zalduondo, L., Cao, X.-F., Chung, D., Golden, J. E., et al. (2025) · Antiviral Research · doi:10.1016/j.antiviral.2025.106206 · Cited by 2 · see citing works
Encephalitic Development in Alphaviral Infection
Paessler, S., & Taylor, K. G. (2011) · InTech eBooks · doi:10.5772/24175 · Cited by 2 · see citing works
Mechanisms of transmission and pathogenesis of alphaviruses
Wang, P. (2026) · Animals and zoonoses. · doi:10.1016/j.azn.2026.05.004
Valero-Cedeño, N., Durán, A., & Mosquera, J. A. (2026) · Reviews in Medical Virology · doi:10.1002/rmv.70165
“The interaction of VEEV with brain cells induces up‐regulation of multiple inflammatory mediators including toll‐like receptor signalling, cytokine‐inducible nitric oxide synthase (iNOS), TNF‐α, transforming growth factor‐beta (TGF‐β), interleukins and chemokines [2, 53, 61, 74, 111, 112].”
Nojoumi, S., Esfandiari, A. H., Azimian, A., Mafinezhad, S., Farsiani, H., & Youssefi, M. (2025) · Archives of Pediatric Infectious Diseases · doi:10.5812/apid-157985
Yun, K., Hurwitz, A., & Perantoni, A. (2018) · PLoS ONE · doi:10.1371/journal.pone.0197356
Oleszak, E., Kuźmak, J., Varadhachary, A. S., & Katsetos, C. (2005) · Experimental Models of Multiple Sclerosis · doi:10.1007/0-387-25518-4_35
- Authors
- Schoneboom, B. A., Catlin, K. M. K., Marty, A. M., & Grieder, F. B.
- Affiliations
- Uniformed Services University of the Health Sciences (US)
- Venue
- Journal of Neuroimmunology
- Publisher
- Elsevier BV
- Published
- 2000-09
- Volume
- 109
- Issue
- 2
- Pages
- 132-146
- ISSN
- 0165-5728 (ISSN-L)
- OpenAlex
- W1982064995
- Cited by
- 86
- References
- 0
- Citations by year
- 2026: 2 · 2025: 7 · 2024: 3 · 2023: 3 · 2022: 1 · 2021: 2 · 2020: 2 · 2019: 7 · 2018: 6 · 2017: 3 · 2016: 3 · 2015: 3 · 2014: 3 · 2013: 3 · 2012: 2
- FWCI
- 3.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroimmunology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uniformed Services University of the Health Sciences
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
- Keywords
- Venezuelan equine encephalitis virus, neuroinflammation, neurodegeneration, meningoencephalitis, inducible nitric oxide synthase, TNF-α, inflammatory cytokines, astrocyte apoptosis, astrocyte activation, knockout mice, attenuated virus strains
- MeSH terms
- Animals, Astrocytes, Brain Edema, Cells, Cultured, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Female, Gliosis, Mice, Inbred C57BL, Nerve Degeneration, Neurons, Phenotype, Tumor Necrosis Factor-alpha, Neuroimmunomodulation, Gene Expression Regulation, Viral, Survival Analysis, Apoptosis, Mice, Knockout, Nitric Oxide Synthase, In Situ Nick-End Labeling, Mice, Nitric Oxide Synthase Type II
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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