Encephalitis in horses refers to inflammation of the brain, which can be caused by various infectious agents, including viruses, bacteria, and parasites. This condition affects the central nervous system and can lead to neurological symptoms such as ataxia, seizures, and changes in behavior. Common viral causes of equine encephalitis include Eastern Equine Encephalitis (EEE), Western Equine Encephalitis (WEE), and West Nile Virus (WNV). Diagnosis often involves clinical evaluation, serological testing, and sometimes cerebrospinal fluid analysis. This page compiles peer-reviewed research studies and scholarly articles that explore the etiology, pathogenesis, clinical presentation, and management of encephalitis in horses.
Gräf T, Rodriguez MC, de Oliveira Brandão Y, Royer CA, do Nascimento Ferreira C, Confortin C, Zanluca C, Strottmann DM, Duarte Dos Santos CN....Rocio virus (ROCV), a neurotropic arbovirus of the genus, caused Brazil’s largest encephalitis outbreak in the 1970s but has since been rarely detected. We report the first ROCV encephalitis clinical case after nearly 40 years and isolated and sequenced the virus from CNS tissue of a horse. Metatranscriptomics enabled full-genome sequencing, revealing divergence from the reference sequence at an evolutionary rate of 5.8–7.0 × 10⁻⁴, consistent with . Thirty-one non-synonymous substitutions were identified, with the envelope protein most affected. Findings indicate ROCV cryptic circula...
Garzaro D, Rodríguez N, Medina G, Alcazar W, Gualdron M, Siem JA, Sulbaran Y, Barrios M, Liprandi F, Jaspe RC, Pujol FH.Madariaga virus (MADV), formerly known as the South American variant of Eastern Equine Encephalitis virus (EEEV), is an alphavirus that belongs to the family and has been periodically infecting equids in Venezuela since its first identification in 1975. This study reports the isolation and molecular characterization of MADV isolated from a horse in December 2024 in the context of MADV cases reported in Venezuela. Methods: Antibodies to the rabies virus were detected by indirect immunofluorescence, and to the Equine Infectious Anemia virus (EIAV) by passive immunodiffusion. MADV RNA was detect...
Wang L, Zheng R, Li Z, Zhang L.Recent increases in cases of western equine encephalitis (WEE) in South America have raised significant concerns about the virus's potential to cause an endemic disease due to its adaptation to mosquito vectors. Currently, there are no effective vaccines or treatments for WEEV, despite ongoing research into various biochemical products in animal models. The virus presents different pathological effects depending on the host. In humans, WEEV infection leads to central nervous system damage, resulting in encephalitis and severe neurological sequelae, which underscores the need for further resear...
In Italy, West Nile virus (WNV) has been consistently causing disease in humans, horses, and birds since 2008; it was initially confined to the northeast of the country and then spread gradually to the western and southern regions. WNV lineage 1 (WNV-L1) virus was the only lineage that circulated in Italy until 2011, but it was progressively replaced by WNV lineage 2 (WNV-L2). WNV disease in humans was not observed in Sicily, southern Italy, until 2016, when the first case of West Nile neuroinvasive disease (WNND) due to WNV-L1 was reported. Our results demonstrate the introduction of WNV-L2 i...
Centers A, Barnaby K, Goedeker S, Pignataro A, Tretyakova I, Lukashevich I, Pushko P, Chung D.There is a need for safe and effective vaccines against the Venezuelan equine encephalitis virus that infects both humans and equines. However, development of a live-attenuated vaccine using the TC-83 strain has been hampered by substantial reactogenicity and the potential for neuroinvasion. In this study, we demonstrate that V4020, a new TC-83-based investigational VEEV vaccine with redundant safety features preventing neuroinvasion and reversion, exhibited no neuroinvasion potential in a murine model. Following subcutaneous or intramuscular administration, a subset of mice that received the ...
Schwarzer A, Ziegler U, Fertey J, Kreuz M, Vahlenkamp TW, Groschup MH, Ulbert S.West Nile virus (WNV), Usutu virus (USUV) and tick-borne encephalitis virus (TBEV) are worldwide endemic zoonotic orthoflaviviruses, often co-circulating in the same areas. Serological studies in animals, mostly birds and horses, are important means to monitor the spread of these viruses and the infection risks for humans. However, cross-reactive antibodies to these structurally similar flaviviruses frequently impact serological differentiation in enzyme-linked immunosorbent assays (ELISAs), hence time-consuming virus neutralization tests (VNTs) have to be employed in laboratories with high bi...
Rakaki ME, van der Walt M, Williams J, Venter M.We detected Shuni virus in horses and ovine fetuses and Shamonda virus in a caprine fetus in South Africa. We identified a Shuni/Shamonda virus reassortant in a horse and Shuni/Caimito, Shamonda/Caimito, and Shamonda/Sango virus reassortants in Culicoides midges. Continued genomic surveillance will be needed to detect orthobunyavirus infections in Africa.
Yu Y, Wang J, Ruan L, Chen L, Khan MZ, You A, Wang C, Li L, Ren H, Wang T, Liu W.Equid alphaherpesvirus type 8 (EHV-8) is a contagious pathogen that causes reproductive disorders, respiratory diseases, and viral encephalitis in equids, resulting in significant economic losses for the global horse and donkey industries. Currently, there are no approved antiviral drugs or vaccines available for EHV-8 control. In this study, we investigated the antiviral efficacy of celastrol against EHV-8 both in vitro and in vivo. Our results demonstrated that celastrol significantly inhibited EHV-8 infection in Rabbit kidney (RK-13) and equine dermal cells (NBL-6) in a dose-dependent manne...
Kordowitzki P.Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus that, among humans, can cause a severe and often fatal illness. The zoonotic EEEV enzootic cycle involves a cycle of transmission between and avian hosts, frequently resulting in spillover to dead-end vertebrate hosts such as humans and horses. Interestingly, it has been described that the W132G mutation of the very low-density lipoprotein receptor (VLDLR), the receptor of EEEV, significantly enhanced the VLDLR-mediated cell attachment of EEEV. The patient's metabolism plays a pivotal role in shaping the complex lan...
Chaintoutis SC, Diakakis N, Polizopoulou ZS, Dovas CI.Serum protein electrophoresis (SPE) is widely used to evaluate protein changes associated with several pathologies, aiming to assist clinical diagnosis. This study aimed to determine, for the first time, SPE profile changes in WNV-naturally infected horses. Sixty horses with different clinical and infection status (encephalitis, asymptomatic infection, and immunologically naïve) were included. Total protein concentrations were determined via an automated biuret method and SPE was performed using a cellulose acetate membrane-based automated system. Statistical analysis revealed significantly h...
Yuen NKY, Harrison JJ, Wang ASW, McMahon IE, Habarugira G, Coyle MP, Bielefeldt-Ohmann H.An incursion and outbreak of Japanese encephalitis virus (JEV) was reported in Australia in 2021 and 2022, respectively. There was speculation that JEV may have been circulating in Australia unknowingly prior to the detection. In this study, we determined sero-prevalence and transmission of West Nile virus (WNV), Murray Valley encephalitis virus (MVEV) and JEV, prior to and post JEV incursion in a sentinel equine population in south-east Queensland (SEQ), Australia, using blocking ELISAs (screening test) and virus neutralisation test (confirmatory). Serum samples collected between 2018 and 202...
Vissani MA, Alamos F, Tordoya MS, Minatel L, Schammas JM, Dus Santos MJ, Trono K, Barrandeguy ME, Balasuriya UBR, Carossino M.Western equine encephalitis virus (WEEV) is a mosquito-borne arbovirus (genus , family ) that has re-emerged in South America in late 2023, causing severe disease in both horses and humans after a nearly 40-year intermission period. We here describe the virological, serological, pathological, and molecular features of WEEV infection in horses during the 2023-2024 outbreak in Argentina. WEEV-infected horses developed neurological signs with mild to severe encephalitis associated with minimal to abundant WEEV-infected cells, as demonstrated by WEEV-specific in situ hybridization. The distributio...
Campos AS, Franco AC, Godinho FM, Huff R, Candido DS, da Cruz Cardoso J, Hua X, Claro IM, Morais P, Franceschina C, de Lima Bermann T, Dos Santos FM....Western equine encephalitis virus (WEEV) is a mosquitoborne virus that reemerged in December 2023 in Argentina and Uruguay, causing a major outbreak. We investigated the outbreak using epidemiologic, entomological, and genomic analyses, focusing on WEEV circulation near the Argentina‒Uruguay border in Rio Grande do Sul state, Brazil. During November 2023‒April 2024, the outbreak in Argentina and Uruguay resulted in 217 human cases, 12 of which were fatal, and 2,548 equine cases. We determined cases on the basis of laboratory and clinical epidemiologic criteria. We characterized 3 fatal equ...
Olofsson KM, van de Velde N, Peletto S, Iulini B, Pratley L, Modabberzadeh B, Małek E, Grandi G.Halicephalobus gingivalis is a nematode with zoonotic potential which can cause fatal opportunistic infections in various mammals. The parasite has never been diagnosed in Sweden, in any species, prior to the presented case. Methods: An imported 21-year-old Icelandic mare developed severe neurological signs. The horse was eventually euthanized and submitted for post-mortem examination where severe lesions in the kidneys were noted. Histopathology revealed the presence of H. gingivalis in both kidneys and the brain. Phylogenetic analysis of the parasite determined it to belong to Lineage 1. Con...
de Heus P, Bagó Z, Weidinger P, Lale D, Trachsel DS, Revilla-Fernández S, Matiasek K, Nowotny N.As evidenced by sero-epidemiological studies, infections of horses with the tick-borne encephalitis virus (TBEV) occur frequently in TBEV-endemic areas. However, there are only very few reports of clinical cases. A possible underreporting may be due to a variety of diagnostic challenges. In this study, ELISA and neutralization tests were applied to serum samples. Brain tissue samples were investigated for the presence of nucleic acids of TBEV, Equid alphaherpesvirus 1, Borna disease virus 1, West Nile and Usutu viruses, rustrela virus, as well as Eastern, Western, and Venezuelan equine encepha...
Kašpárková N, Bártová E, Žákovská A, Budíková M, Sedlák K.Lyme disease, caused by some strains of bacterial spirochetes Borrelia burgdorferi sensu lato (Bbsl), affects humans but also domestic animals including horses. The primary pathogens in horses in Europe are B. afzelii, B. garinii and B. burgdorferi sensu stricto. To our knowledge, there are no data available on the seropositivity of B. burgdorferi s.l. in horses from the Czech Republic. In this country, horses are mainly used for sport, breeding, and recreational riding in areas where vectors of B. burgdorferi s.l. are present, which is why they are frequently at risk of infection. The aim of ...
Topp AK, Springer A, Mischke R, Rieder J, Feige K, Ganter M, Nagel-Kohl U, Nordhoff M, Boelke M, Becker S, Pachnicke S, Schunack B, Dobler G, Strube C.Tick-borne encephalitis virus (TBEV) is a tick-transmitted flavivirus, which can infect humans and animals, sometimes even with a fatal outcome. Since many decades, TBEV is endemic in southern Germany, while only sporadic occurrence has been noted in northern parts of the country so far. Nevertheless, autochthonous human clinical cases are increasing in the federal state of Lower Saxony in north-western Germany, and several natural foci of TBEV transmission have recently been detected in this federal state. In order to shed more light on the current distribution of TBEV in Lower Saxony, the pr...
Langsjoen RM, Key A, Shariatzadeh N, Jackson CR, Mahmood F, Arkun K, Alexandrescu S, Solomon IH, Piantadosi A.Eastern equine encephalitis virus (EEEV) is a relatively little-studied alphavirus that can cause devastating viral encephalitis, potentially leading to severe neurological sequelae or death. Although case numbers have historically been low, outbreaks have been increasing in frequency and scale since the 2000 s. It is critical to investigate EEEV evolutionary patterns, especially within human hosts, to understand patterns of emergence, host adaptation, and within-host evolution. To this end, we obtained formalin-fixed paraffin-embedded tissue blocks from discrete brain regions from five contem...
Hill V, Koch RT, Bialosuknia SM, Ngo K, Zink SD, Koetzner CA, Maffei JG, Dupuis AP, Backenson PB, Oliver J, Bransfield AB, Misencik MJ, Petruff TA....Eastern equine encephalitis virus (EEEV) causes a rare but severe disease in horses and humans and is maintained in an enzootic transmission cycle between songbirds and Culiseta melanura mosquitoes. In 2019, the largest EEEV outbreak in the United States for more than 50 years occurred, centered in the Northeast. To explore the dynamics of the outbreak, we sequenced 80 isolates of EEEV and combined them with existing genomic data. We found that, similar to previous years, cases were driven by multiple independent but short-lived virus introductions into the Northeast from Florida. Once in the ...
Anderson C, Baha H, Boghdeh N, Barrera M, Alem F, Narayanan A.Zoonotic pathogens that are vector-transmitted have and continue to contribute to several emerging infections globally. In recent years, spillover events of such zoonotic pathogens have increased in frequency as a result of direct contact with livestock, wildlife, and urbanization, forcing animals from their natural habitats. Equines serve as reservoir hosts for vector-transmitted zoonotic viruses that are also capable of infecting humans and causing disease. From a One Health perspective, equine viruses, therefore, pose major concerns for periodic outbreaks globally. Several equine viruses ha...
Cao X, Yang D, Parvathareddy J, Chu YK, Kim EJ, Fitz-Henley JN, Li X, Lukka PB, Parmar KR, Temrikar ZH, Dhole P, Adcock RS, Gabbard J, Bansal S....Venezuelan and eastern equine encephalitis viruses (VEEV and EEEV, respectively) are mosquito-borne, neuroinvasive human pathogens for which no FDA-approved therapeutic exists. Besides the biothreat posed by these viruses when aerosolized, arthropod transmission presents serious health risks to humans, as demonstrated by the 2019 outbreak of EEE disease in the United States that resulted in 38 confirmed cases, 19 deaths, and neurological effects in survivors. Here, we describe the discovery of a 2-pyrrolidinoquinazolinone scaffold, efficiently synthesized in two to five steps, whose structural...
Bonilla-Aldana DK, Bonilla Carvajal CD, Moreno-Ramos E, Barboza JJ, Rodriguez-Morales AJ.Eastern equine encephalitis virus (EEEV) and Venezuelan equine encephalitis virus (VEEV) viruses are zoonotic pathogens affecting humans, particularly equines. These neuroarboviruses compromise the central nervous system and can be fatal in different hosts. Both have significantly influenced Colombia; however, few studies analyse its behaviour, and none develop maps using geographic information systems to characterise it. To describe the temporal-spatial distribution of those viruses in Colombia between 2008 and 2019. Retrospective cross-sectional descriptive study, based on weekly reports by ...
Wang H, Liu S, Lv Y, Wei W.Venezuelan equine encephalitis virus (VEEV) is an emerging zoonotic virus in the alphavirus genus. It can be transmitted to humans due to spillover from equid-mosquito cycles. The symptoms caused by VEEV include fever, headache, myalgia, nausea, and vomiting. It can also cause encephalitis in severe cases. The evolutionary features of VEEV are largely unknown. In this study, we comprehensively analyzed the codon usage pattern of VEEV by computing a variety of indicators, such as effective number of codons (ENc), codon adaptation index (CAI), relative synonymous codon usage (RSCU), on 130 VEEV ...
Luethy D.The continued recognition and emergence of alphavirus and flavivirus diseases is a growing veterinary and public health concern. As the global environment continues to change, mosquito-borne diseases will continue to evolve and expand. Continued development of readily available vaccines for the prevention of these diseases in humans and animals is essential to controlling epizootics of these diseases. Further research into effective antiviral treatments is also sorely needed. This article describes equine encephalitis viruses with a focus on clinical and public health considerations.
Cardo MV, Carbajo AE, Mozzoni C, Kliger M, Vezzani D.Blood feeding patterns of mosquitoes are a key component in the dynamics of arboviral encephalitides transmission. In temperate Argentina, the members of the Culex pipiens complex include Cx. pipiens molestus, Cx. quinquefasciatus and their hybrids. To characterize their blood feeding patterns, adult resting mosquitoes were collected monthly during the warm season in urban and rural equestrian fields. The availability of birds and domestic mammals per site was characterized. The blood source and the complex member were successfully identified for 89 specimens using PCR. Blood of 19 vertebrate ...
Fukushi N, Fukushi H.Equine herpesvirus type 1 (EHV-1) is a devastating pathogen of horses, their natural hosts, and causes fatal encephalitis in non-natural hosts. We previously demonstrated that acylation of the tegument protein UL11 is required for viral replication in cultured cells. We created a mutant virus (EHV-1 UL12 trunc UL11 G2AC7AC9A), in which glycyl and cysteinyl residues at positions 2, 7 and 9 of UL11 that are normally acylated were replaced with alanyl residues. This virus, designated the 2/7/9 mutant, has a limited-replication cycle (LRC), in which replication stops after just a few cycles. Here,...
Pillai VV, Mudd LJ, Sola MF.A 19-y-old American Saddlebred gelding was evaluated for epiphora of the right eye and generalized cachexia. Initial examination revealed anterior uveitis without ulceration, for which treatment was initiated. Despite the initial response to treatment, the signs progressively worsened to blindness. Histologic examination of the enucleated eye revealed granulomatous panuveitis and optic neuritis with intralesional nematode larvae identified as . Over time and despite anthelmintic treatment, blindness developed in the left eye along with neurologic signs, and the horse was euthanized. Disseminat...
Dürrwald R, Kolodziejek J, Oh DY, Herzog S, Liebermann H, Osterrieder N, Nowotny N.(1) Background: Vaccination of horses and sheep against Borna disease (BD) was common in endemic areas of Germany in the 20th century but was abandoned in the early 1990s. The recent occurrence of fatal cases of human encephalitis due to Borna disease virus 1 (BoDV-1) has rekindled the interest in vaccination. (2) Methods: The full genomes of the BD live vaccine viruses "Dessau" and "Giessen" were sequenced and analyzed for the first time. All vaccination experiments followed a proof-of-concept approach. Dose-titration infection experiments were performed in rabbits, based on both cell culture...
Cavalleri JV, Korbacska-Kutasi O, Leblond A, Paillot R, Pusterla N, Steinmann E, Tomlinson J.Horses and other equids can be infected with several viruses of the family Flaviviridae, belonging to the genus Flavivirus and Hepacivirus. This consensus statement focuses on viruses with known occurrence in Europe, with the objective to summarize the current literature and formulate clinically relevant evidence-based recommendations regarding clinical disease, diagnosis, treatment, and prevention. The viruses circulating in Europe include West Nile virus, tick-borne encephalitis virus, Usutu virus, Louping ill virus and the equine hepacivirus. West Nile virus and Usutu virus are mosquito-bor...
Chalhoub FLL, Horta MAP, Alcantara LCJ, Morales A, Dos Santos LMB, Guerra-Campos V, Rodrigues CDS, Santos CC, Mares-Guia MAM, Pauvolid-Corrêa A....Infections with arboviruses are reported worldwide. Saint Louis encephalitis (SLEV) and West Nile (WNV) viruses are closely related flaviviruses affecting humans and animals. SLEV has been sporadically detected in humans, and corresponding antibodies have been frequently detected in horses throughout Brazil. WNV was first reported in western Brazil over a decade ago, has been associated with neurological disorders in humans and equines and its prevalence is increasing nationwide. Herein, we investigated by molecular and serological methods the presence of SLEV and WNV in equines from Rio de Ja...
Zeller HG, Schuffenecker I.West Nile (WN) virus is a mosquito-transmitted flavivirus. It is widely distributed in Africa, the Middle East, Asia, and southern Europe and was recently introduced to North America. Birds are involved in the cycle of transmission as amplifying hosts. Humans and horses are considered accidental dead-end hosts. WN fever was initially considered a minor arbovirosis, usually inducing a nonsymptomatic or a mild flu-like illness in humans, but some cases of encephalitis associated with fatalities were reported in Israel in the 1950s. After two silent decades, several human and equine outbreaks of ...
Calisher CH.Of more than 500 arboviruses recognized worldwide, 5 were first isolated in Canada and 58 were first isolated in the United States. Six of these viruses are human pathogens: western equine encephalitis (WEE) and eastern equine encephalitis (EEE) viruses (family Togaviridae, genus Alphavirus), St. Louis encephalitis (SLE) and Powassan (POW) viruses (Flaviviridae, Flavivirus), LaCrosse (LAC) virus (Bunyaviridae, Bunyavirus), and Colorado tick fever (CTF) virus (Reoviridae, Coltivirus). Their scientific histories, geographic distributions, virology, epidemiology, vectors, vertebrate hosts, transm...
O'Sullivan JD, Allworth AM, Paterson DL, Snow TM, Boots R, Gleeson LJ, Gould AR, Hyatt AD, Bradfield J.In September, 1994, an outbreak of severe respiratory disease affected 18 horses, their trainer, and a stablehand in Queensland, Australia. Fourteen horses and one human being died. A novel virus was isolated from those affected and named equine morbillivirus (EMV). We report a case of encephalitis caused by this virus. Results: A 35-year-old man from Queensland had a brief aseptic meningitic illness in August, 1994, shortly after caring for two horses that died from EMV infection and then assisting at their necropsies. He then suffered severe encephalitis 13 months later, characterised by unc...
Murgue B, Murri S, Zientara S, Durand B, Durand JP, Zeller H.On September 6, 2000, two cases of equine encephalitis caused by West Nile (WN) virus were reported in southern France (Hérault Province), near Camargue National Park, where a WN outbreak occurred in 1962. Through November 30, 76 cases were laboratory confirmed among 131 equines with neurologic disorders. The last confirmed case was on November 3, 2000. All but three cases were located in a region nicknamed "la petite Camargue," which has several large marshes, numerous colonies of migratory and resident birds, and large mosquito populations. No human case has been confirmed among clinically ...
Murray KO, Mertens E, Despres P.Zoonotic West Nile virus (WNV) circulates in natural transmission cycles involving certain mosquitoes and birds, horses, humans, and a range of other vertebrates are incidental hosts. Clinical infections in humans can range in severity from uncomplicated WNV fever to fatal meningoencephalitis. Since its introduction to the Western Hemisphere in 1999, WNV had spread across North America, Central and South America and the Caribbean, although the vast majority of severe human cases have occurred in the United States of America (USA) and Canada. By 2002-2003, the WNV outbreaks have involved thousa...
Steele KE, Twenhafel NA.The encephalitides caused by Venezuelan (VEEV), eastern (EEEV), and western (WEEV) equine encephalitis viruses are important natural diseases of horses and humans and potential agents of biowarfare or bioterrorism. No licensed vaccines or specific therapies exist to prevent or treat human infections with VEEV, EEEV, or WEEV. Well-characterized animal models are needed to support the development of such medical countermeasures under the United States Food and Drug Administration's "Animal Rule." This review focuses on the pathological features and pathogenetic mechanisms of these alphaviral enc...
Frost MJ, Zhang J, Edmonds JH, Prow NA, Gu X, Davis R, Hornitzky C, Arzey KE, Finlaison D, Hick P, Read A, Hobson-Peters J, May FJ, Doggett SL....To determine the cause of an unprecedented outbreak of encephalitis among horses in New South Wales, Australia, in 2011, we performed genomic sequencing of viruses isolated from affected horses and mosquitoes. Results showed that most of the cases were caused by a variant West Nile virus (WNV) strain, WNV(NSW2011), that is most closely related to WNV Kunjin (WNV(KUN)), the indigenous WNV strain in Australia. Studies in mouse models for WNV pathogenesis showed that WNV(NSW2011) is substantially more neuroinvasive than the prototype WNV(KUN) strain. In WNV(NSW2011), this apparent increase in vir...
Rivas F, Diaz LA, Cardenas VM, Daza E, Bruzon L, Alcala A, De la Hoz O, Caceres FM, Aristizabal G, Martinez JW, Revelo D, De la Hoz F, Boshell J....In 1995, the first Venezuelan equine encephalitis (VEE) outbreak in Colombia in 22 years caused an estimated 75,000 human cases, 3000 with neurologic complications and 300 fatal, in La Guajira State. Of the state's estimated 50,000 equines, 8% may have died. An epizootic IC virus, probably introduced from Venezuela, was rapidly amplified among unvaccinated equines. Record high rainfall, producing high densities of vector Aedes taeniorhynchus, led to extensive epidemic transmission (30% attack rate) in the four affected municipalities. Native Wayuu Indians, constituting 24% of the state's popul...
Russo AT, White MA, Watowich SJ.Alphavirus replication and propagation is dependent on the protease activity of the viral nsP2 protein, which cleaves the nsP1234 polyprotein replication complex into functional components. Thus, nsP2 is an attractive target for drug discovery efforts to combat highly pathogenic alphaviruses. Unfortunately, antiviral development has been hampered by a lack of structural information for the nsP2 protease. Here, we report the crystal structure of the nsP2 protease (nsP2pro) from Venezuelan equine encephalitis alphavirus determined at 2.45 A resolution. The protease structure consists of two dist...
Carrera JP, Forrester N, Wang E, Vittor AY, Haddow AD, López-Vergès S, Abadía I, Castaño E, Sosa N, Báez C, Estripeaut D, Díaz Y, Beltrán D....The eastern equine encephalitis (EEE) and Venezuelan equine encephalitis (VEE) viruses are pathogens that infect humans and horses in the Americas. Outbreaks of neurologic disease in humans and horses were reported in Panama from May through early August 2010. Methods: We performed antibody assays and tests to detect viral RNA and isolate the viruses in serum samples from hospitalized patients. Additional cases were identified with enhanced surveillance. Results: A total of 19 patients were hospitalized for encephalitis. Among them, 7 had confirmed EEE, 3 had VEE, and 1 was infected with both ...
Morales MA, Barrandeguy M, Fabbri C, Garcia JB, Vissani A, Trono K, Gutierrez G, Pigretti S, Menchaca H, Garrido N, Taylor N, Fernandez F, Levis S....West Nile virus (WNV) was isolated from the brains of 3 horses that died from encephalitis in February 2006. The horses were from different farms in central Argentina and had not traveled outside the country. This is the first isolation of WNV in South America.
Gosztonyi G, Ludwig H.Natural BD is a nonpurulent acute/subacute encephalitis of horses and sheep with a propensity to involve the olfactory and limbic systems, and the brain stem. The inflammation is concentrated primarily in the gray matter, but subcortical white matter may also be affected. Experimental BD can be produced in a series of animals from birds to primates. The neuropathology after experimental infection is similar to that in natural disease but the inflammatory changes are more diffuse. In the rat and mouse, a persistent/tolerant infection can also be induced, in which inflammatory changes are conspi...
Arrigo NC, Adams AP, Weaver SC.The eastern equine encephalitis (EEE) complex consists of four distinct genetic lineages: one that circulates in North America (NA EEEV) and the Caribbean and three that circulate in Central and South America (SA EEEV). Differences in their geographic, pathogenic, and epidemiologic profiles prompted evaluation of their genetic diversity and evolutionary histories. The structural polyprotein open reading frames of all available SA EEEV and recent NA EEEV isolates were sequenced and used in evolutionary and phylogenetic analyses. The nucleotide substitution rate per year for SA EEEV (1.2 x 10(-4...
Niller HH, Angstwurm K, Rubbenstroth D, Schlottau K, Ebinger A, Giese S, Wunderlich S, Banas B, Forth LF, Hoffmann D, Höper D, Schwemmle M, Tappe D....In 2018-19, Borna disease virus 1 (BoDV-1), the causative agent of Borna disease in horses, sheep, and other domestic mammals, was reported in five human patients with severe to fatal encephalitis in Germany. However, information on case frequencies, clinical courses, and detailed epidemiological analyses are still lacking. We report the occurrence of BoDV-1-associated encephalitis in cases submitted to the Institute of Clinical Microbiology and Hygiene, Regensburg University Hospital, Regensburg, Germany, and provide a detailed description of newly identified cases of BoDV-1-induced encephali...
Komar N.West Nile virus (WNV) has emerged in recent years in temperate regions of Europe and North America, presenting a threat to both public and animal health. The most serious manifestation of infection is fatal encephalitis in humans and horses, as well as mortality in certain domestic and wild birds. A recent development in the epizootiology of this mosquito-borne flavivirus was the occurrence of a severe outbreak in New York City and surrounding areas. During this outbreak, mortality was observed in humans, horses, a cat and numerous species of wild birds, particularly members of the family Corv...
Suen WW, Prow NA, Hall RA, Bielefeldt-Ohmann H.West Nile virus (WNV) is an important emerging neurotropic virus, responsible for increasingly severe encephalitis outbreaks in humans and horses worldwide. However, the mechanism by which the virus gains entry to the brain (neuroinvasion) remains poorly understood. Hypotheses of hematogenous and transneural entry have been proposed for WNV neuroinvasion, which revolve mainly around the concepts of blood-brain barrier (BBB) disruption and retrograde axonal transport, respectively. However, an over‑representation of in vitro studies without adequate in vivo validation continues to obscure our...
Marfin AA, Gubler DJ.In 1999, an epidemic of West Nile virus (WNV) encephalitis occurred in New York City (NYC) and 2 surrounding New York counties. Simultaneously, an epizootic among American crows and other bird species occurred in 4 states. Indigenous transmission of WNV had never been documented in the western hemisphere until this epidemic. In 2000, the epizootic expanded to 12 states and the District of Columbia, and the epidemic continued in NYC, 5 New Jersey counties, and 1 Connecticut county. In addition to these outbreaks, several large epidemics of WNV have occurred in other regions of the world where t...
Lobigs M, Pavy M, Hall RA, Lobigs P, Cooper P, Komiya T, Toriniwa H, Petrovsky N.Advax is a polysaccharide-based adjuvant that potently stimulates vaccine immunogenicity without the increased reactogenicity seen with other adjuvants. This study investigated the immunogenicity of a novel Advax-adjuvanted Vero cell culture candidate vaccine against Japanese encephalitis virus (JEV) in mice and horses. The results showed that, in mice, a two-immunization, low-dose (50 ng JEV antigen) regimen with adjuvanted vaccine produced solid neutralizing immunity comparable to that elicited with live ChimeriVax-JE immunization and superior to that elicited with tenfold higher doses of a ...
McLean RG, Ubico SR, Bourne D, Komar N.WN virus is one of the most ubiquitous arboviruses occurring over a broad geographical range and in a wide diversity of vertebrate host and vector species. The virus appears to be maintained in endemic foci on the African continent and is transported annually to temperate climates to the north in Europe and to the south in South Africa. Reports of clinical disease due to natural WN virus infection in wild or domestic animals were much less common than reports of infection (virus isolation or antibody detection). Until recently, records of morbidity and mortality in wild birds were confined to ...
Huang ZY, de Boer WF, van Langevelde F, Olson V, Blackburn TM, Prins HH.Hosts species for multi-host pathogens show considerable variation in the species' reservoir competence, which is usually used to measure species' potential to maintain and transmit these pathogens. Although accumulating research has proposed a trade-off between life-history strategies and immune defences, only a few studies extended this to host species' reservoir competence. Using a phylogenetic comparative approach, we studied the relationships between some species' life-history traits and reservoir competence in three emerging infectious vector-borne disease systems, namely Lyme disease, W...
Angenvoort J, Brault AC, Bowen RA, Groschup MH.West Nile virus (WNV) is a flavivirus transmitted between certain species of birds and mosquito vectors. Tangential infections of equids and subsequent equine epizootics have occurred historically. Although the attack rate has been estimated to be below 10%, mortality rates can approach 50% in horses that present clinical disease. Symptoms are most commonly presenting in the form of encephalitis with ataxia as well as limb weakness, recumbency and muscle fasciculation. The most effective strategy for prevention of equine disease is proper vaccination with one of the numerous commercially avail...
Venter M, Swanepoel R.West Nile virus (WNV) is widely distributed in South Africa, but since a few cases of neurological disease have been reported from this region, endemic lineage 2 strains were postulated to be of low virulence. Several cases of nonfatal encephalitis in humans as well as fatal cases in a foal, dog, and ostrich chicks have, however, been associated with lineage 2 WNV in South Africa. The pathogenesis of lineage 2 WNV strains was investigated using mouse neuroinvasive experiments, gene expression experiments, and genome sequence comparisons which indicated that lineage 2 strains that are highly pa...
Shirato K, Kimura T, Mizutani T, Kariwa H, Takashima I.West Nile (WN) virus is a mosquito-borne flavivirus that can cause lethal encephalitis in humans and horses. The WN virus endemic in New York City (NY) in 1999 caused large-scale mortality of wild birds that was not evident in endemic areas in other parts of the world, and the pathogenesis of the WN virus strain isolated in NY (NY strain) appears to differ from that of previously isolated strains. However, the pathogenesis of NY strain infection remains unclear. This study examined CC (RANTES/CCL5, MIP-1 alpha/CCL3, MIP-1 beta/CCL4) and CXC (IP-10/CXCL10, B lymphocyte chemoattractant (BLC/CXCL...
Hannaman D, Dupuy LC, Ellefsen B, Schmaljohn CS.Venezuelan equine encephalitis virus (VEEV), a mosquito-borne alphavirus, causes periodic epizootics in equines and is a recognized biological defense threat for humans. There are currently no FDA-licensed vaccines against VEEV. We developed a candidate DNA vaccine expressing the E3-E2-6K-E1 genes of VEEV (pWRG/VEE) and performed a Phase 1 clinical study to assess the vaccine's safety, reactogenicity, tolerability, and immunogenicity when administered by intramuscular (IM) or intradermal (ID) electroporation (EP) using the Ichor Medical Systems TriGrid™ Delivery System. Subjects in IM-EP gro...
Ostlund EN, Crom RL, Pedersen DD, Johnson DJ, Williams WO, Schmitt BJ.After the 1999 outbreak of West Nile (WN) encephalitis in New York horses, a case definition was developed that specified the clinical signs, coupled with laboratory test results, required to classify cases of WN encephalitis in equines as either probable or confirmed. In 2000, 60 horses from seven states met the criteria for a confirmed case. The cumulative experience from clinical observations and diagnostic testing during the 1999 and 2000 outbreaks of WN encephalitis in horses will contribute to further refinement of diagnostic criteria.
Baer A, Lundberg L, Swales D, Waybright N, Pinkham C, Dinman JD, Jacobs JL, Kehn-Hall K.Venezuelan equine encephalitis virus (VEEV) is a previously weaponized arthropod-borne virus responsible for causing acute and fatal encephalitis in animal and human hosts. The increased circulation and spread in the Americas of VEEV and other encephalitic arboviruses, such as eastern equine encephalitis virus and West Nile virus, underscore the need for research aimed at characterizing the pathogenesis of viral encephalomyelitis for the development of novel medical countermeasures. The host-pathogen dynamics of VEEV Trinidad donkey-infected human astrocytoma U87MG cells were determined by car...
Greene IP, Paessler S, Austgen L, Anishchenko M, Brault AC, Bowen RA, Weaver SC.Epidemics of Venezuelan equine encephalitis (VEE) result from high-titer equine viremia of IAB and IC subtype viruses that mediate increased mosquito transmission and spillover to humans. Previous genetic studies suggest that mutations in the E2 envelope glycoprotein allow relatively viremia-incompetent, enzootic subtype ID strains to adapt for equine replication, leading to VEE emergence. To test this hypothesis directly, chimeric VEEV strains containing the genetic backbone of enzootic subtype ID strains and the partial envelope glycoprotein genes of epizootic subtype IC and IAB strains, as ...
