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Topic:Alphavirus
Alphaviruses are a group of viruses transmitted primarily by mosquitoes and are known to cause disease in horses and humans. In equine populations, alphaviruses such as Eastern Equine Encephalitis Virus (EEEV), Western Equine Encephalitis Virus (WEEV), and Venezuelan Equine Encephalitis Virus (VEEV) are of particular concern due to their ability to cause severe neurological disease. Infection in horses can lead to symptoms ranging from fever and lethargy to more severe signs such as ataxia, paralysis, and encephalitis, often resulting in high mortality rates. Understanding the transmission dynamics, pathogenesis, and immune response in horses is crucial for developing effective prevention and control strategies. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, clinical presentation, diagnosis, and management of alphavirus infections in horses, as well as advancements in vaccine development and vector control methods.
Human and Equine Infection with Alphaviruses and Flaviviruses in Panamá during 2010: A Cross-Sectional Study of Household Contacts during an Encephalitis Outbreak. Members of the genera (family ) and (family ) are important zoonotic human and equine etiologic agents of neurologic diseases in the New World. In 2010, an outbreak of Madariaga virus (MADV; formerly eastern equine encephalitis virus) and Venezuelan equine encephalitis virus (VEEV) infections was reported in eastern Panamá. We further characterized the epidemiology of the outbreak by studying household contacts of confirmed human cases and of equine cases with neurological disease signs. Serum samples were screened using a hemagglutination inhibition test, and human results were confirmed u...
Alphaviruses: Serological Evidence of Human Infection in Paraguay (2012-2013). Alphaviruses can produce febrile illness and encephalitis in dead-end hosts such as horses and humans. Within this genus, the Venezuelan Equine Encephalitis virus (VEEV) complex includes pathogenic epizootic subtypes and enzootic subtypes that are not pathogenic in horses (except subtype IE, Mexican strains), although they can cause febrile symptoms in humans. The Rio Negro virus (RNV-VEEV subtype VI) circulates in Argentina, where it was associated with undifferentiated febrile illness. Mayaro (MAYV) and Una (UNAV) viruses belong to a different group, the Semliki Forest virus complex, with co...
Cryptic etiopathological conditions of equine nervous system with special emphasis on viral diseases. The importance of horse (Equus caballus) to equine practitioners and researchers cannot be ignored. An unevenly distributed population of equids harbors numerous diseases, which can affect horses of any age and breed. Among these, the affections of nervous system are potent reason for death and euthanasia in equids. Many episodes associated with the emergence of equine encephalitic conditions have also pose a threat to human population as well, which signifies their pathogenic zoonotic potential. Intensification of most of the arboviruses is associated with sophisticated interaction between ve...
Mutation of Asn-475 in the Venezuelan Equine Encephalitis Virus nsP2 Cysteine Protease Leads to a Self-Inhibited State. The alphaviral nsP2 cysteine protease of the Venezuelan equine encephalitis virus (VEEV) is a validated antiviral drug target. Clan CN proteases contain a cysteine protease domain that is intimately packed with an S-adenosyl-l-methionine-dependent RNA methyltransferase (SAM MTase) domain. Within a cleft formed at the interface of these two domains, the peptide substrate is thought to bind. The nucleophilic cysteine can be found within a conserved motif, NVCWAK, which differs from that of papain (CGSCWAFS). Mutation of the motif residue, N475, to alanine unexpectedly produced a self-inhibited s...
Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas. Venezuelan equine encephalitis (VEE) complex alphaviruses are important re-emerging arboviruses that cause life-threatening disease in equids during epizootics as well as spillover human infections. We conducted a comprehensive analysis of VEE complex alphaviruses by sequencing the genomes of 94 strains and performing phylogenetic analyses of 130 isolates using complete open reading frames for the nonstructural and structural polyproteins. Our analyses confirmed purifying selection as a major mechanism influencing the evolution of these viruses as well as a confounding factor in molecular cloc...
A Quantitative Real-Time RT-PCR Assay for the Detection of Venezuelan equine encephalitis virus Utilizing a Universal Alphavirus Control RNA. (VEEV) is an from the family that causes epizootic outbreaks in equids and humans in Central and South America. So far, most studies use conventional reverse transcriptase PCR assays for the detection of the different VEEV subtypes. Here we describe the development of a TaqMan quantitative real-time reverse transcriptase PCR assay for the specific detection and quantitation of all VEEV subtypes which uses in parallel a universal equine encephalitis virus control RNA carrying target sequences of the three equine encephalitis viruses. The control RNA was used to generate standard curves for t...
Complete Genome Sequencing and Phylogenetic Analysis of a Getah Virus Strain (Genus Alphavirus, Family Togaviridae) Isolated from Culex tritaeniorhynchus Mosquitoes in Nagasaki, Japan in 2012. Getah virus (GETV; genus Alphavirus, family Togaviridae) is a mosquito-borne virus known to cause disease in horses and pigs. In 2014, for the first time in ∼30 years, a sudden GETV outbreak occurred among racehorses in Ibaraki, Japan. Two years before this outbreak, we obtained multiple GETV isolates from Culex tritaeniorhynchus mosquitoes collected in Nagasaki, Japan and determined the whole genome sequence of GETV isolate 12IH26. Our phylogenetic analysis of GETV strains revealed that the isolate 12IH26 forms a robust clade with the epidemic strains 14-I-605-C1 and 14-I-605-C2 isolated fr...
Culex Tarsalis Mosquitoes as Vectors of Highlands J Virus. Highlands J virus (HJV) is an alphavirus closely related to western equine encephalitis virus (WEEV) and eastern equine encephalitis virus (EEEV). HJV is an avian pathogen with the potential for disruption of poultry operations, but is not known to cause human or equine disease. HJV has only been identified in the eastern United States and is thought to have a transmission cycle similar to that of EEEV involving Culiseta melanura mosquitoes and birds. However, HJV is more genetically similar to WEEV and it remains unclear if it may be transmitted by Culex species mosquitoes like WEEV. Seven st...
A Phase 1 clinical trial of a DNA vaccine for Venezuelan equine encephalitis delivered by intramuscular or intradermal electroporation. 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...
Characterization of Genetic Variability of Venezuelan Equine Encephalitis Viruses. Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, an...
[EPIDEMIOLOGIC ANALYSIS OF OUTBREAKS OF DISEASES CAUSED BY AMERICAN EQUINE ENCEPHALITIS CAUSATIVE AGENTS IN ENDEMIC REGIONS]. Epidemiologic analysis of epidemic outbreaks caused by American equine encephalitis causative agents is carried out in the review. Eastern equine encephalomyelitis (EEE), Western equine encephalomyelitis (WEE) and Venezuela equine encephalomyelitis (VEE) viruses are etiologic agents of dangerous transmissive diseases that are usually accompanied by fever and neurologic symptoms. Among the New World alphaviruses, VEE virus has the most potential danger for humans and domestic animals. Currently, enzootic strains of VEE play an increasing role as etiologic agents of human diseases. Most of the V...
Recent vaccine technology in industrial animals. Various new technologies have been applied for developing vaccines against various animal diseases. Virus-like particle (VLP) vaccine technology was used for manufacturing the porcine circovirus type 2 and RNA particle vaccines based on an alphavirus vector for porcine epidemic diarrhea (PED). Although VLP is classified as a killed-virus vaccine, because its structure is similar to the original virus, it can induce long-term and cell-mediated immunity. The RNA particle vaccine used a Venezuela equine encephalitis (VEE) virus gene as a vector. The VEE virus partial gene can be substituted with ...
Venezuelan Equine Encephalitis Virus Induces Apoptosis through the Unfolded Protein Response Activation of EGR1. 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...
Diversity and ecology survey of mosquitoes potential vectors in Belgian equestrian farms: A threat prevention of mosquito-borne equine arboviruses. Emergence of West Nile Virus was recently recorded in several European countries, which can lead to severe health problems in horse populations. Europe is also at risk of introduction of mosquito-borne equine alphavirus from Americas. Prevention of these arboviruses requires a clear understanding of transmission cycles, especially their vectors. To characterize mosquito fauna, their ecology and identify potential vectors of equine arboviruses in Belgium, entomological surveys of six equestrian farms located in the Wolloon Region were conducted during 2011-2012. The harvest of mosquitoes was ba...
Alphaviral equine encephalomyelitis (Eastern, Western and Venezuelan). Summary Alphaviral equine encephalomyelitis is a mosquito-borne infection that causes severe neurological disease and fatalities in horses and humans in the Americas. Consequently, the equine alphaviruses (Eastern, Western and Venezuelan) are of considerable concern worldwide and are notifiable to the World Organisation for Animal Health. In addition, these diseases are considered a potent potential biological weapon, emphasising the need to develop an effective vaccine. Alphaviral equine encephalomyelitis is caused by Eastern equine encephalomyelitis virus (EEEV), Western equine encephalomyel...
Sindbis and Middelburg Old World Alphaviruses Associated with Neurologic Disease in Horses, South Africa. Old World alphaviruses were identified in 52 of 623 horses with febrile or neurologic disease in South Africa. Five of 8 Sindbis virus infections were mild; 2 of 3 fatal cases involved co-infections. Of 44 Middelburg virus infections, 28 caused neurologic disease; 12 were fatal. Middelburg virus likely has zoonotic potential.
Melatonin, minocycline and ascorbic acid reduce oxidative stress and viral titers and increase survival rate in experimental Venezuelan equine encephalitis. Venezuelan equine encephalitis (VEE) virus causes an acute central nervous system infection in human and animals. Melatonin (MLT), minocycline (MIN) and ascorbic acid (AA) have been shown to have antiviral activities in experimental infections; however, the mechanisms involved are poorly studied. Therefore, the aim of this study was to determine the effects of those compounds on the viral titers, NO production and lipid peroxidation in the brain of mice and neuroblastoma cultures infected by VEE virus. Infected mouse (10 LD50) were treated with MLT (500 μg/kg bw), MIN (50mg/kg bw) or AA (50mg...
Ross River Virus (RRV) infection in horses and humans: a review. A fascinating and important arbovirus is Ross River Virus (RRV) which is endemic and epizootic in nature in certain parts of the world. RRV is a member of the genus Alphavirus within the Semliki Forest complex of the family Togaviridae, which also includes the Getah virus. The virus is responsible for causing disease both in humans as well as horses. Mosquito species (Aedes camptorhynchus and Aedes vigilax; Culex annulirostris) are the most important vector for this virus. In places of low temperature as well as low rainfall or where there is lack of habitat of mosquito there is also limitatio...
The ubiquitin proteasome system plays a role in venezuelan equine encephalitis virus infection. Many viruses have been implicated in utilizing or modulating the Ubiquitin Proteasome System (UPS) to enhance viral multiplication and/or to sustain a persistent infection. The mosquito-borne Venezuelan equine encephalitis virus (VEEV) belongs to the Togaviridae family and is an important biodefense pathogen and select agent. There are currently no approved vaccines or therapies for VEEV infections; therefore, it is imperative to identify novel targets for therapeutic development. We hypothesized that a functional UPS is required for efficient VEEV multiplication. We have shown that at non-tox...
Neutralising antibodies for Mayaro virus in Pantanal, Brazil. The Pantanal hosts diverse wildlife species and therefore is a hotspot for arbovirus studies in South America. A serosurvey for Mayaro virus (MAYV), eastern (EEEV), western (WEEV) and Venezuelan (VEEV) equine encephalitis viruses was conducted with 237 sheep, 87 free-ranging caimans and 748 equids, including 37 collected from a ranch where a neurologic disorder outbreak had been recently reported. Sera were tested for specific viral antibodies using plaque-reduction neutralisation test. From a total of 748 equids, of which 264 were immunised with vaccine composed of EEEV and WEEV and 484 had n...
Combined alphavirus replicon particle vaccine induces durable and cross-protective immune responses against equine encephalitis viruses. Alphavirus replicons were evaluated as potential vaccine candidates for Venezuelan equine encephalitis virus (VEEV), western equine encephalitis virus (WEEV), or eastern equine encephalitis virus (EEEV) when given individually or in combination (V/W/E) to mice or cynomolgus macaques. Individual replicon vaccines or the combination V/W/E replicon vaccine elicited strong neutralizing antibodies in mice to their respective alphavirus. Protection from either subcutaneous or aerosol challenge with VEEV, WEEV, or EEEV was demonstrated out to 12 months after vaccination in mice. Individual replicon v...
Novel indole-2-carboxamide compounds are potent broad-spectrum antivirals active against western equine encephalitis virus in vivo. Neurotropic alphaviruses, including western, eastern, and Venezuelan equine encephalitis viruses, cause serious and potentially fatal central nervous system infections in humans for which no currently approved therapies exist. We previously identified a series of thieno[3,2-b]pyrrole derivatives as novel inhibitors of neurotropic alphavirus replication, using a cell-based phenotypic assay (W. Peng et al., J. Infect. Dis. 199:950-957, 2009, doi:http://dx.doi.org/10.1086/597275), and subsequently developed second- and third-generation indole-2-carboxamide derivatives with improved potency, solub...
Discovery of a novel compound with anti-venezuelan equine encephalitis virus activity that targets the nonstructural protein 2. Alphaviruses present serious health threats as emerging and re-emerging viruses. Venezuelan equine encephalitis virus (VEEV), a New World alphavirus, can cause encephalitis in humans and horses, but there are no therapeutics for treatment. To date, compounds reported as anti-VEEV or anti-alphavirus inhibitors have shown moderate activity. To discover new classes of anti-VEEV inhibitors with novel viral targets, we used a high-throughput screen based on the measurement of cell protection from live VEEV TC-83-induced cytopathic effect to screen a 340,000 compound library. Of those, we identified...
Eastern equine encephalitis cases among horses in Brazil between 2005 and 2009. Eastern equine encephalitis is a viral zoonosis that exhibits complex distribution and epidemiology, and greater importance should be given to this disease by the public-health authorities. In Brazil, although eastern equine encephalitis virus (EEEV) has been identified in vectors and antibodies are sometimes detected in horses and humans, there have been no records of equine encephalitis in horses caused by this virus during the last 24 years. This study describes eighteen cases of eastern equine encephalomyelitis that occurred in six Brazilian states between 2005 and 2009. Viral RNA was iden...
A risk index model for predicting eastern equine encephalitis virus transmission to horses in Florida. A GIS-based risk index model was developed to quantify EEEV transmission risk to horses in the State of Florida. EEEV is a highly pathogenic arbovirus that is endemic along the east coast of the United States, and it is generally fatal to both horses and humans. The model evaluates EEEV transmission risk at individual raster cells in map on a continuous scale of 0 to 1. The risk index is derived based on local habitat features and the composition and configuration of surrounding land cover types associated with EEEV transmission. The model was verified and validated using the locations of docu...
Novel vaccination approaches against equine alphavirus encephalitides. The current production of inactivated vaccines for the prevention of equine alphavirus encephalitides caused by Eastern, Western and Venezuelan Equine Encephalitis viruses (EEEV, WEEV, VEEV) involves the manipulation of large quantities of infectious viral particles under biosafety level 3 containment laboratories with the potential risk of transmission to the operators. Moreover, these vaccines are not capable of inducing a long-lasting immunity. Modified live vaccines, which were also attempted, maintain residual virulence and neurotropism, causing disease in both horses and humans. Therefor...
Eastern equine encephalitis in Latin America. 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 ...
Pathogenesis of Venezuelan equine encephalitis. Equine encephalids have high mortality rates and represent a significant zoonotic public health threat. Of these the most pathogenic viruses to equids are the alphaviruses in the family Togaviridae. The focus of this review Venezualen equine encephalitis virus (VEEV) has caused the most widespread and recent epidemic outbreaks of disease. Circulation in naturally occuring rodent-mosquito cycles, results in viral spread to both human and equine populations. However, equines develop a high titer viremia and can transmit the virus back to mosquito populations. As such, the early recognition and c...
Venezuelan equine encephalitis replicon particles can induce rapid protection against foot-and-mouth disease virus. We have previously shown that delivery of the porcine type I interferon gene (poIFN-α/β) with a replication-defective human adenovirus vector (adenovirus 5 [Ad5]) can sterilely protect swine challenged with foot-and-mouth disease virus (FMDV) 1 day later. However, the need of relatively high doses of Ad5 limits the applicability of such a control strategy in the livestock industry. Venezuelan equine encephalitis virus (VEE) empty replicon particles (VRPs) can induce rapid protection of mice against either homologous or, in some cases, heterologous virus challenge. As an alternative approach ...
