Cited by 465Mosquito-borne diseases and controlViral Infections and VectorsVector-Borne Animal Diseases

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V ENEZUELAN E QUINE E NCEPHALITIS

Weaver, Scott C., Ferro, Cristina, Barrera, Roberto, Boshell, Jorge, Navarro, Juan-Carlos·2004·Annual Review of Entomology

DOI 10.1146/annurev.ento.49.061802.123422

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Abstract

▪ Abstract Venezuelan equine encephalitis virus (VEEV) remains a naturally emerging disease threat as well as a highly developed biological weapon. Recently, progress has been made in understanding the complex ecological and viral genetic mechanisms that coincide in time and space to generate outbreaks. Enzootic, equine avirulent, serotype ID VEEV strains appear to alter their serotype to IAB or IC, and their vertebrate and mosquito host range, to mediate repeated VEE emergence via mutations in the E2 envelope glycoprotein that represent convergent evolution. Adaptation to equines results in highly efficient amplification, which results in human disease. Although epizootic VEEV strains are opportunistic in their use of mosquito vectors, the most widespread outbreaks appear to involve specific adaptation to Ochlerotatus taeniorhynchus, the most common vector in many coastal areas. In contrast, enzootic VEEV strains are highly specialized and appear to utilize vectors exclusively in the Spissipes section of the Culex (Melanoconion) subgenus.

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“Incubation is typically 2-5 days, and acute disease persists for 4-6 days; occasionally the disease becomes biphasic 4-8 days later with neurological and systemic involvement such as brain hemorrhaging and edema, necrotizing vasculitis, lymphocyte destruction, neutrophilic infiltration, and neuronal degradation (Weave…”
Background
Tumour Necrosis Factor-α, Chemokines, and Leukocyte Infiltrate Are Biomarkers for Pathology in the Brains of Venezuelan Equine Encephalitis (VEEV)-Infected Mice
Phelps, 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
“This is representative of systemic VEEV infection and aligns well with other research [30–32], whereby the systemic infection is readily resolved by the host, but is the “springboard” from which the virus accesses the brain [41].”
Result
Ecological aspects of mosquitoes (Diptera: Culicidae) in a fragment of seasonal dry tropical forest (Caatinga) in Brazil
Freire, R. C. D. M., Barbosa, T. D. M., Jales, J., Ximenes, M. D. F. F. D. M., la Corte, R., & Gama, R. (2021) · Journal of Arid Environments · doi:10.1016/j.jaridenv.2021.104528 · Cited by 12
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Gynandromorphs in mosquitoes (Diptera: Culicidae) from Valle del Cauca, Colombia.
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Everglades virus: an underrecognized disease-causing subtype of Venezuelan equine encephalitis virus endemic to Florida, USA
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Advancements in organs-on-chips technology for viral disease and anti-viral research
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Bivalent single domain antibody constructs for effective neutralization of Venezuelan equine encephalitis
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Improving the DNA Barcode Library of Mosquito Species With New Identifications and Discoveries in North-Central Argentina
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“In Florida, and elsewhere in the Neotropics, Melanoconion mosquitoes are important vectors of VEE virus [6].”
Background
Mosquito Fauna in Home Environments of Tabasco, Mexico
Torres-Chablé, O., Baak-Baak, C., Cigarroa-Toledo, N., Zaragoza-Vera, C., Arjona-Jiménez, G., Moreno-Perez, L. G., Machaín-Williams, C., & García-Rejón, J. (2017) · The Southwestern entomologist · doi:10.3958/059.042.0416 · Cited by 11
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“Eretmapodites chrysogaster Uganda (1944) (Smithburn et al., 1948)”
BackgroundInfluential
The Main Arboviruses and Virus Detection Methods in Vectors: Current Approaches and Future Perspectives
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“The VEE complex consists of seven species and numerous subvariants [31], with its distribution varying across the New World.”
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“Alphaviruses, which encompass the Venezuelan equine encephalitis virus (VEEV), eastern equine encephalitis virus (EEEV), and western equine encephalitis virus (WEEV), are part of the Togaviridae family and are characterized as single-stranded, positive-sense RNA viruses [168].”
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Arbovirus infection increases the risk for the development of neurodegenerative disease pathology in the murine model
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“In humans, VEEV typically leads to flu-like illness, ranging from mild to severe encephalitis and neurological symptoms such as seizures, drowsiness, and confusion (Weaver et al., 2004).”
Background
Neurological manifestations of encephalitic alphaviruses, traumatic brain injuries, and organophosphorus nerve agent exposure
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Molecular Tracking of the Origin of Vesicular Stomatitis Outbreaks in 2004 and 2018, Ecuador
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“that the genetic diversity of the West Nile virus depended on the mosquito species [56,57].”
BackgroundSelf-citation
Mosquito-borne viral diseases and potential transmission blocking vaccine candidates.
Bakhshi, H., Failloux, A., Zakeri, S., Raz, A., & Dinparast-Djadid, N. (2018) · Infection, Genetics and Evolution · doi:10.1016/j.meegid.2018.05.023 · Cited by 9
Medical Importance of Mosquitoes
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The Economic Impact of High Consequence Zoonotic Pathogens: Why Preparing for these is a Wicked Problem
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Combinations of approved oral nucleoside analogues confer potent suppression of alphaviruses in vitro and in vivo
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Design principles and applications of synthetic self‐replicating RNAs
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“Larger RNA viruses, for example, from the families of Togaviridae (e.g., VEEV) and Flaviviridae (e.g., Hepacivirus HCV) (9.0 – 13 kb) encode the fully active RdRP complex in their genome, split across multiple genes in a single polyprotein ORF (Chase, 2022; Weaver et al., 2004).”
BackgroundInfluential
PERK Is Critical for Alphavirus Nonstructural Protein Translation
Dahal, B., Lehman, C., Akhrymuk, I., Bracci, N. R., Panny, L., Barrera, M. D., Bhalla, N., Jacobs, J. L., Dinman, J. D., & Kehn-Hall, K. (2021) · Viruses · doi:10.3390/v13050892 · Cited by 8
Retracted
Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose
Rossi, S., Russell-Lodrigue, K., Plante, K., Bergren, N. A., Gorchakov, R., Roy, C., & Weaver, S. (2020) · Vaccines · doi:10.3390/vaccines8030497 · Cited by 8
Self-citation
Susceptibility of Psorophora confinnis (Diptera: Culicidae) to Infection with Epizootic (Subtype IC) and Enzootic (Subtype ID) Venezuelan Equine Encephalitis Viruses
Ortiz, D. I., Anishchenko, M., & Weaver, S. C. (2005) · Journal of Medical Entomology · doi:10.1093/jmedent/42.5.857 · Cited by 24
Self-citation
Alphaviral Encephalitides
Weaver, S. C., & Paessler, S. (2009) · Elsevier eBooks · doi:10.1016/b978-0-12-369408-9.00021-4 · Cited by 11
Self-citation
CHAPTER 20 – Equine Alphaviruses
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Evaluation of long-term preservation methods for viral RNA in mosquitoes at room temperature
Kai, I., Kobayashi, D., Itokawa, K., Sanjoba, C., Itoyama, K., & Isawa, H. (2024) · Journal of Virological Methods · doi:10.1016/j.jviromet.2024.114887 · Cited by 7
Therapeutic efficacy of a potent anti-Venezuelan equine encephalitis virus antibody is contingent on Fc effector function
Schwedler, J. L., Stefan, M. A., Thatcher, C. E., McIlroy, P. R., Sinha, A., Phillips, A. M., Sumner, C. A., Courtney, C. M., Kim, C. Y., Weilhammer, D. R., et al. (2024) · mAbs · doi:10.1080/19420862.2023.2297451 · Cited by 8
“3 In addition, VEEV can be easily produced in large volumes and can spread by aerosol or transdermal inoculation (e.g., a mosquito bite).”
Sequence Diversity in the 3′ Untranslated Region of Alphavirus Modulates IFIT2-Dependent Restriction in a Cell Type-Dependent Manner
Hickson, S. E., Brekke, E., Schwerk, J., Saluhke, I., Zaver, S., Woodward, J. J., Savan, R., & Hyde, J. (2021) · bioRxiv · doi:10.1089/jir.2024.0229 · Cited by 7
“VEEV subtypes exhibit genetic 424 diversity and can be divided into different lineages, with epizootic strains being further classified 425 into clades [1].”
Influential
General Aspects on Arboviruses
Contigiani, M., Diaz, L. A., & Spinsanti, L. (2017) · Springer eBooks · doi:10.1007/978-3-319-13884-8_5 · Cited by 7
The antiviral BDGR-49 provides protection from lethal, neurotropic Venezuelan equine encephalitis virus intranasal infection in mice
Williams, E. P., Xue, Y., Vogel, P., Yang, D., Flores, A. B., Li, X., Ogorek, T. J., Saini, M., Iulek, J., Ruiz, F. X., et al. (2025) · Journal of Virology · doi:10.1128/jvi.01679-24 · Cited by 6
Insect-Specific Chimeric Viruses Potentiated Antiviral Responses and Inhibited Pathogenic Alphavirus Growth in Mosquito Cells
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“affecting humans and equines, can cause fatal encephalitis (4).”
Background
Arboviral Equine Encephalitides
Toribio, R. E. (2022) · Veterinary Clinics of North America Equine Practice · doi:10.1016/j.cveq.2022.04.004 · Cited by 6
Live-Attenuated VEEV Vaccine Delivered by iDNA Using Microneedles Is Immunogenic in Rabbits
Tretyakova, I., Tomai, M., Vasilakos, J., & Pushko, P. (2022) · Frontiers in Tropical Diseases · doi:10.3389/fitd.2022.813671 · Cited by 6
“Climate, ecological changes, and international travel increase the risk of VEEV reemergence (3-5).”
Background
Viral Zoonoses: Wildlife Perspectives
Milton, A. A. P., Priya, G. B., Ghatak, S., & Das, S. (2020) · Livestock diseases and management · doi:10.1007/978-981-15-2651-0_15 · Cited by 7
T Lymphocytes as Measurable Targets of Protection and Vaccination Against Viral Disorders
Monette, A., & Mouland, A. J. (2018) · International review of cytology · doi:10.1016/bs.ircmb.2018.07.006 · Cited by 7
“More recent outbreaks in Mexico and South America are behind the classification of VEEV as a re-emerging disease (Weaver et al., 2004) .”
Background
Existen condiciones que favorecen la reaparición del virus de la encefalitis equina venezolana en la Alta Guajira colombiana
Ferro, C., Salas, J. D. L., González, M., Díaz, A., Cabrera, C., Flórez, Z., Duque, M. C., Lugo, L., & Bello, B. (2014) · doi:10.7705/biomedica.v35i1.2212 · Cited by 6
“Los niveles de viremia en los humanos son similares a los registrados en los equinos, pero se considera que los humanos no son tan eficientes como amplificadores del virus porque están menos expuestos a las picaduras de los vectores (1,3,8).”
BackgroundInfluentialSelf-citation
Synthesis of 3-heteroaryl-pyrrolo[2,3-b]pyridines as potent inhibitors of AP-2-associated protein kinase 1 (AAK1) with antiviral activity.
Ravi, N. P., Eynde, W. V., Karim, M., Tran, D. H. N., Agrawal, A., Schols, D., Voet, A., Einav, S., Dehaen, W., & de Jonghe, S. (2024) · European journal of medicinal chemistry · doi:10.1016/j.ejmech.2024.116967 · Cited by 5
Single-Dose Immunogenic DNA Vaccines Coding for Live-Attenuated Alpha- and Flaviviruses
Pushko, P., Lukashevich, I. S., Johnson, D. M., & Tretyakova, I. (2024) · Viruses · doi:10.3390/v16030428 · Cited by 5
“Climate, ecological changes, commerce, and international travel increase the risk of virus re-emergence [69,101,106].”
Background
Application of In Silico and HTS Approaches to Identify Nuclear Import Inhibitors for Venezuelan Equine Encephalitis Virus Capsid Protein: A Case Study
Shechter, S., Thomas, D. R., & Jans, D. A. (2020) · Frontiers in Chemistry · doi:10.3389/fchem.2020.573121 · Cited by 6
“Venezuelan equine encephalitis virus (VEEV) is a single-stranded RNA virus of the genus Alphavirus (Weaver and Barrett, 2004; Weaver et al., 2004).”
Background
Microbead electrochemiluminescence immunoassay for detection and identification of Venezuelan equine encephalitis virus.
Dai, X., Hilsen, R. E., Hu, W.-G., & Fulton, R. (2010) · Journal of Virological Methods · doi:10.1016/j.jviromet.2010.07.022 · Cited by 5
Complete nucleotide sequences of the small and medium RNA genome segments of Kairi virus (family Bunyaviridae)
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Brilacidin as a Broad-Spectrum Inhibitor of Enveloped, Acutely Infectious Viruses
Anderson, C. A., Barrera, M. D., Boghdeh, N. A., Smith, M., Alem, F., & Narayanan, A. (2023) · Microorganisms · doi:10.3390/microorganisms12010054 · Cited by 4
“The alphaviruses Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are spread to humans through mosquitos and can cause symptoms such as fever, rash, joint pain, inflammation, and malaise [2].”
Background
Advances in computational approaches to structure determination of alphaviruses and flaviviruses using cryo-electron microscopy.
Lata, K., Charles, S., & Prasad, V. M. (2023) · Journal of Structural Biology · doi:10.1016/j.jsb.2023.107993 · Cited by 4
Predicting potential transmission risk of Everglades virus in Florida using mosquito blood meal identifications
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“However, several other muroid rodent species are the natural hosts of EVEV and other enzootic subtypes of VEEV distributed throughout the Americas (14, 20).”
Background
Predicting the potential distribution of Culex (Melanoconion) cedecei in Florida and the Caribbean using ecological niche models.
Sloyer, K. E., Burkett-Cadena, N., & Campbell, L. (2022) · Journal of Vector Ecology · doi:10.52707/1081-1710-47.1.88 · Cited by 4
Arboviral Central Nervous System Infections
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Interactions between the imperiled West Indian manatee, Trichechus manatus, and mosquitoes (Diptera: Culicidae) in Everglades National Park, Florida, USA
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Structural Characterization and Formulation Development of a Trivalent Equine Encephalitis Virus-Like Particle Vaccine Candidate.
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Animal health risk of legally imported exotic animals into the Netherlands in the period 2013–2014
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The fine line between protection and pathology in neurotropic flavivirus and alphavirus infections
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VEEV TC-83 Triggers Dysregulation of the Tryptophan–Kynurenine Pathway in the Central Nervous System That Correlates with Cognitive Impairment in Tg2576 Mice
Fongsaran, C., Dineley, K. T., Paessler, S., & Cisneros, I. E. (2024) · Pathogens · doi:10.3390/pathogens13050397 · Cited by 3
“In human cases of VEEV infection, approximately 4–14% of patients report neurological complications including seizures, photophobia, behavioral changes, neuromuscular weakness, and paralysis [5,6].”
Background
Demonstration of in vivo efficacy, cryo-EM-epitope identification, and breadth of two anti-alphavirus bispecific single domain antibodies
Gardner, C. L., Pletnev, S., Liu, J. L., Anderson, G., Shriver-Lake, L., Bylund, T., Green, C., Stephens, T., Sutton, M. S., Tsybovsky, Y., et al. (2025) · Journal of Virology · doi:10.1128/jvi.01875-25 · Cited by 3
“Although not usually fatal in humans ( 1%), VEEV has a high morbidity rate due to the subclinical to clinical ratio being 1:1, can cause neurological disease in 4%–14% of cases, and is fatal in 19%–83% of equine cases (15).”
RNA structures within Venezuelan equine encephalitis virus E1 alter macrophage replication fitness and contribute to viral emergence
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Detection of Aedes Scapularis In Southwestern Florida.
Heinig, R., Morreale, R., Reeves, L. E., Lloyd, A., Hoel, D. F., & Lucas, K. J. (2023) · Journal of the American Mosquito Control Association · doi:10.2987/23-7146 · Cited by 3
Inhibition of Venezuelan Equine Encephalitis Virus Using Small Interfering RNAs
Haikerwal, A., Barrera, M. D., Bhalla, N., Zhou, W., Boghdeh, N. A., Anderson, C., Alem, F., & Narayanan, A. (2022) · Viruses · doi:10.3390/v14081628 · Cited by 3
Ecological Characterization of Mosquitoes (Diptera: Culicidae) at the Southern Coast of Mar Chiquita Lake, Argentina
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“In addition, mosquito-borne arboviruses can affect cattle (Weaver et al. 2004) as well as wildlife including some bird species (Díaz et al.”
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Arbovirus Adaptation: Roles in Transmission and Emergence
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“Specifically, typical epizootic VEEV strains of the subtypes IAB and IC are efficiently transmitted by this mosquito (Weaver et al., 2004).”
Background
Animal Health: Ectoparasites
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Arthropod-Borne Viral Encephalitis
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Authors: Weaver, S. C., Ferro, C., Barrera, R., Boshell, J., & Navarro, J.-C.
Affiliations: Instituto Nacional de Salud (CO)
Centers for Disease Control and Prevention (US)
Center for Biodefense and Emerging Infectious Diseases and Department of Pathology, University of Texas Medical Branch, Galveston, Texas 77555-0609;
ORCID: Weaver, Scott C.
Barrera, Roberto
Navarro, Juan-Carlos
Venue: Annual Review of Entomology
Publisher: Annual Reviews
Published: 2004-01
Volume: 49
Issue: 1
Pages: 141-174
ISSN: 0066-4170 (ISSN-L)
1545-4487
DOI: 10.1146/annurev.ento.49.061802.123422
OpenAlex: W2123164501
Cited by: 465
References: 158
Citations by year: 2026: 16 · 2025: 16 · 2024: 16 · 2023: 24 · 2022: 21 · 2021: 24 · 2020: 29 · 2019: 26 · 2018: 21 · 2017: 20 · 2016: 25 · 2015: 14 · 2014: 22 · 2013: 16 · 2012: 19
FWCI: 2.83
Type: journal article
Language: en
Open access: closed
Locations: Annual Review of Entomology (publishedVersion)
PubMed (publishedVersion)
Funders: Departamento Administrativo de Ciencia, Tecnología e Innovación (COLCIENCIAS)
National Institutes of Health (5r03tw005919-03, n01ai25489-12-0-1)
National Institute of Allergy and Infectious Diseases (R01AI049725, AI49725-01, AI-25489, R01AI048807, AI48807-01)
Fogarty International Center (TW5919)
Topics: Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Mosquito-borne diseases and control
Health Sciences › Medicine › Infectious Diseases › Viral Infections and Vectors
Life Sciences › Immunology and Microbiology › Virology › Vector-Borne Animal Diseases
Keywords: Venezuelan equine encephalitis virus, emerging infectious diseases, biological weapons, serotype switching, E2 glycoprotein, convergent evolution, host range adaptation, mosquito vectors, Culex (Melanoconion), epizootic strains, viral outbreak, arbovirus ecology
MeSH terms: Aedes, Animals, Disease Outbreaks, Encephalitis Virus, Venezuelan Equine, Encephalomyelitis, Venezuelan Equine, Horse Diseases, Horses, Host-Parasite Interactions, Humans, Insect Vectors, Mutation, Viral Envelope Proteins, Viral Vaccines, Virulence, Equidae

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