Serology testing performed on this virus has shown the presence of six different subtypes (classified I to VI).1 These have been given names, including Mucambo, Tonate, and Pixuna subtypes. There are seven different variants in subtype I, and three of these variants, A, B, and C are the epizootic strains.
The Mucambo virus (subtype III) appears to have evolved ~1807 AD (95% credible interval: 1559–1944).2 In Venezuela the Mucambo subtype was identified in 1975 by Jose Esparza and J. Sánchez using cultured mosquito cells.3
In the Americas, there have been 21 reported outbreaks of Venezuelan equine encephalitis virus.4 Outbreaks occurred in Central American and South American countries. This virus was isolated in 1938, and outbreaks have been reported in many different countries since then. Mexico, Colombia, Venezuela, and the United States are just some of the countries that have reported outbreaks.5 Outbreaks of VEE generally occur after periods of heavy precipitation that cause mosquito populations to thrive.6
Between December 1992 and January 1993, the Venezuelan state of Trujillo experienced an outbreak of this virus. Overall, 28 cases of the disease were reported along with 12 deaths. June 1993 saw a bigger outbreak in the Venezuelan state of Zulia, as 55 humans died as well as 66 equine deaths.7
A much larger outbreak in Venezuela and Colombia occurred in 1995. On May 23, 1995, equine encephalitis-like cases were reported in the northwest portion of the country. Eventually, the outbreak spread more towards the north as well as to the south. The outbreak caused about 11,390 febrile cases in humans as well as 16 deaths. About 500 equine cases were reported with 475 deaths.89
An outbreak of this disease occurred in Colombia in September 1995. This outbreak resulted in 14,156 human cases that were attributable to Venezuelan equine encephalitis virus with 26 human deaths.10 A possible explanation for the serious outbreaks was the particularly heavy rain that had fallen. This could have caused increased numbers of mosquitoes that could serve as vectors for the disease. A more likely explanation is that deforestation caused a change in mosquito species. Culex taenopius mosquitos, which prefer rodents, were replaced by Aedes taeniorhynchus mosquitoes, which are more likely to bite humans and large equines.
Though the majority of VEE outbreaks occur in Central and South America, the virus has potential to outbreak again in the United States. It has been shown the invasive mosquito species Aedes albopictus is a viable carrier of VEE virus.11
Oxatomide has shown antiviral activity against VEE virus in cell culture.12 Oxatomide is an over the counter drug and an H1 antihistamine. H1 antihistamines characteristically cause drowsiness (e.g., Benadryl) and cross the blood-brain barrier. To date, oxatomide has not been tested in humans or animals for the treatment of VEE. Oxatomide is still sold in Japan (Sawai Pharmaceutical).13
There is an inactivated vaccine containing the C-84 strain for VEE virus that is used to immunize horses. Another vaccine, containing the TC-83 strain, is used on humans in military and laboratory positions who risk contracting the virus. The human vaccine can result in side effects and does not fully immunize the patient. The TC-83 strain was generated by passing the virus 83 times through a guinea pig heart cell culture; C-84 is a derivative of TC-83.14 Alphaviral genomes lacking the full set of structural proteins are currently being used to produce self-amplifying mRNA vaccines and may be useful for delivering therapeutic enzymes and proteins in the future.15
In April 2009, the U.S. Army Medical Research Institute of Infectious Diseases at Fort Detrick reported that samples of Venezuelan equine encephalitis virus were discovered missing during an inventory of a group of samples left by a departed researcher. The report stated the samples were likely among those destroyed when a freezer malfunctioned.16
During the Cold War, both the United States biological weapons program and the Soviet biological weapons program researched and weaponized VEE.17 In his book Biohazard: The Chilling True Story of the Largest Covert Biological Weapons Program in the World, author Stephen Handelman details the weaponization of VEE and other biologicals including plague, anthrax, and smallpox, by Dr. Ken Alibek in the Cold War Soviet weapons programs.
Vlak, Just M. (July 2007). "Gernot H. Bergold (1911–2003)". Journal of Invertebrate Pathology. 95 (3): 231–232. Bibcode:2007JInvP..95..231V. doi:10.1016/j.jip.2007.03.015. /wiki/Bibcode_(identifier) ↩
Auguste, Albert J.; Volk, Sara M.; Arrigo, Nicole C.; Martinez, Raymond; Ramkissoon, Vernie; Adams, A. Paige; Thompson, Nadin N.; Adesiyun, Abiodun A.; Chadee, Dave D.; Foster, Jerome E.; Travassos Da Rosa, Amelia P.A.; Tesh, Robert B.; Weaver, Scott C.; Carrington, Christine V.F. (September 2009). "Isolation and phylogenetic analysis of Mucambo virus (Venezuelan equine encephalitis complex subtype IIIA) in Trinidad". Virology. 392 (1): 123–130. doi:10.1016/j.virol.2009.06.038. PMC 2804100. PMID 19631956. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2804100 ↩
Esparza, J.; Sánchez, A. (June 1975). "Multiplication of Venezuelan Equine Encephalitis (Mucambo) virus in cultured mosquito cells". Archives of Virology. 49 (2–3): 273–280. doi:10.1007/BF01317545. PMID 813617. S2CID 20202029. /wiki/Doi_(identifier) ↩
Weaver, Scott C.; Ferro, Cristina; Barrera, Roberto; Boshell, Jorge; Navarro, Juan-Carlos (7 January 2004). "Venezuelan equine encephalitis". Annual Review of Entomology. 49 (1): 141–174. doi:10.1146/annurev.ento.49.061802.123422. PMID 14651460. /wiki/Doi_(identifier) ↩
Osorio, Jorge E.; Yuill, Thomas M. (2017). "Venzuelan Equine Encephalitis". In Beran, George W. (ed.). Handbook of zoonoses. Vol. Section B Viral Zoonoses. CRC Press. ISBN 9781351441797.[page needed] 9781351441797 ↩
Rico-Hesse, R; Weaver, S C; de Siger, J; Medina, G; Salas, R A (6 June 1995). "Emergence of a new epidemic/epizootic Venezuelan equine encephalitis virus in South America". Proceedings of the National Academy of Sciences of the United States of America. 92 (12): 5278–5281. Bibcode:1995PNAS...92.5278R. doi:10.1073/pnas.92.12.5278. PMC 41677. PMID 7777497. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC41677 ↩
Acha, Pedro N.; Szyfres, Boris (2001). Zoonoses and Communicable Diseases Common to Man and Animals: Chlamydioses, rickettsioses, and viroses. Pan American Health Org. ISBN 978-92-75-11580-0.[page needed] 978-92-75-11580-0 ↩
Beaman, Joseph R.; Turell, Michael J. (1 January 1991). "Transmission of Venezuelan Equine Encephalomyelitis Virus by Strains of Aedes albopictus (Diptera: Culicidae) Collected in North and South America". Journal of Medical Entomology. 28 (1): 161–164. doi:10.1093/jmedent/28.1.161. PMID 2033608. /wiki/Doi_(identifier) ↩
Hu, X; Morazzani, E; Compton, JR; Harmon, M; Soloveva, V; Glass, PJ; Garcia, AD; Marugan, JJ; Legler, PM (2023). "In Silico Screening of Inhibitors of the Venezuelan Equine Encephalitis Virus Nonstructural Protein 2 Cysteine Protease". Viruses. 15 (7): 1503. doi:10.3390/v15071503. hdl:10919/115936. PMC 10385868. PMID 37515189. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10385868 ↩
"Oxatomide Tablets 30mg Sawai: 100 tablets". mimaki-family-japan.com. Retrieved December 10, 2024. https://www.mimaki-family-japan.com/item/detail?item_prefix=TF&item_code=002434&item_branch=001 ↩
"Venezuelan equine encephalitis virus". https://microbewiki.kenyon.edu/index.php/Venezuelan_equine_encephalitis_virus ↩
Azizi, H; Renner, TM; Agbayani, G; Simard, B; Dudani, R; Harrison, BA; Iqbal, U; Jia, Y; McCluskie, J; Akache, B (2024). "Self-amplifying RNAs generated with the modified nucleotides 5-methylcytidine and 5-methyluridine mediate strong expression and immunogenicity in vivo". NAR Molecular Medicine. 1 (2): ugae004. doi:10.1093/narmme/ugae004. https://academic.oup.com/narmolmed/article/1/2/ugae004/7642858 ↩
Shaughnessy, Larry (22 April 2009). "Army: 3 vials of virus samples missing from Maryland facility". CNN. http://edition.cnn.com/2009/US/04/22/missing.virus.sample/index.html ↩
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