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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.
Codon usage bias of Venezuelan equine encephalitis virus and its host adaption. 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 ...
Eastern, Western, and Venezuelan Equine Encephalitis and West Nile Viruses: Clinical and Public Health Considerations. 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.
Advances in the Development of Small Molecule Antivirals against Equine Encephalitic Viruses. Venezuelan, western, and eastern equine encephalitic alphaviruses (VEEV, WEEV, and EEEV, respectively) are arboviruses that are highly pathogenic to equines and cause significant harm to infected humans. Currently, human alphavirus infection and the resulting diseases caused by them are unmitigated due to the absence of approved vaccines or therapeutics for general use. These circumstances, combined with the unpredictability of outbreaks-as exemplified by a 2019 EEE surge in the United States that claimed 19 patient lives-emphasize the risks posed by these viruses, especially for aerosolized V...
Epidemiological and Genomic Characterisation of Middelburg and Sindbis Alphaviruses Identified in Horses with Febrile and Neurological Infections, South Africa (2014-2018). Although Old World alphaviruses, Middelburg- (MIDV) and Sindbis virus (SINV), have previously been detected in horses and wildlife with neurologic disease in South Africa, the pathogenesis and clinical presentation of MIDV and SINV infections in animals are not well documented. Clinical samples from horses across South Africa with acute or fatal neurologic and febrile infections submitted between 2014-2018 were investigated. In total, 69/1084 (6.36%) and 11/1084 (1.01%) horses tested positive for MIDV and SINV, respectively, by real-time reverse transcription (RT) PCR. Main signs/outcomes for ...
Epidemiological Study of Multiple Zoonotic Mosquito-Borne Alphaviruses in Horses in Queensland, Australia (2018-2020). The increased frequency of extreme weather events due to climate change has complicated the epidemiological pattern of mosquito-borne diseases, as the host and vector dynamics shift to adapt. However, little is known about the seroprevalence of common mosquito-borne virus infections in horses in Australia. In this study, serological surveys for multiple alphaviruses were performed on samples taken from 622 horses across two horse populations (racehorses and horses residing on The University of Queensland (UQ) campus) in Queensland using the gold standard virus neutralization test. As is the ca...
Getah Virus (Alphavirus): An Emerging, Spreading Zoonotic Virus. Getah virus (GETV) is a zoonotic virus transmitted by mosquitoes, belonging to the family, genus. It was first isolated from mosquitoes in Malaysia in 1955, being widespread in island countries in the South Pacific region. Since the beginning of the 21st century, GETV expanded its range and geographical distribution from low-latitude tropical regions to 60° north latitude, being isolated from 17 different species of mosquitoes belonging to five genera of Culicidae (, , , and ), as well as from midges in Eurasia. Molecular genetic evolution analysis revealed large molecular differences betw...
Arboviral Equine Encephalitides. A number of viruses transmitted by biological vectors or through direct contact, air, or ingestion cause neurologic disease in equids. Of interest are viruses of the Togaviridae, Flaviviridae, Rhabdoviridae, Herpesviridae, Bornaviridae, and Bunyaviridae families. Many are classified as arboviruses because they use arthropod vectors, whereas others are transmitted directly via ingestion, inhalation, or integument damage. The goal of this article is to provide an overview on pathophysiologic and clinical aspects of arboviruses of equine importance, including alphaviruses (Togaviridae) and flaviv...
Inhibition of Venezuelan Equine Encephalitis Virus Using Small Interfering RNAs. Acutely infectious new world alphaviruses such as Venezuelan Equine Encephalitis Virus (VEEV) pose important challenges to the human population due to a lack of effective therapeutic intervention strategies. Small interfering RNAs that can selectively target the viral genome (vsiRNAs) has been observed to offer survival advantages in several in vitro and in vivo models of acute virus infections, including alphaviruses such as Chikungunya virus and filoviruses such as Ebola virus. In this study, novel vsiRNAs that targeted conserved regions in the nonstructural and structural genes of the VEEV ...
Eastern Equine Encephalitis Virus Taxonomy, Genomics, and Evolution. Eastern equine encephalitis virus (EEEV; Togaviridae, Alphavirus) is an arthropod-borne virus (arbovirus) primarily maintained in an enzootic cycle between Culiseta melanura (Coquillett) and passerine birds. EEEV, which has the highest reported case- fatality rate among arbovirus in the Americas, is responsible for sporadic outbreaks in the Eastern and Midwest United States. Infection is associated with severe neurologic disease and mortality in horses, humans, and other vertebrate hosts. Here, we review what is known about EEEV taxonomy, functional genomics, and evolution, and identify gaps i...
Ecology of Eastern Equine Encephalitis Virus in the Southeastern United States: Incriminating Vector and Host Species Responsible for Virus Amplification, Persistence, and Dispersal. Eastern equine encephalitis virus (EEEV; family Togaviridae, genus Alphavirus) is a mosquito-borne pathogen found in eastern North America that causes severe disease in humans and horses. The mosquito Culiseta melanura (Coquillett) (Diptera: Culicidae) is the primary enzootic vector of EEEV throughout eastern North America while several mosquito species belonging to diverse genera serve as bridge vectors. The ecology of EEEV differs between northern and southern foci, with respect to phenology of outbreaks, important vertebrate hosts, and bridge vector species. Active transmission is limited t...
Exposing cryptic epitopes on the Venezuelan equine encephalitis virus E1 glycoprotein prior to treatment with alphavirus cross-reactive monoclonal antibody allows blockage of replication early in infection. Eastern equine encephalitis virus (EEEV), western equine encephalitis virus (WEEV) and Venezuelan equine encephalitis virus (VEEV) can cause fatal encephalitis in humans and equids. Some MAbs to the E1 glycoprotein are known to be cross-reactive, weakly neutralizing in vitro but can protect from disease in animal models. We investigated the mechanism of neutralization of VEEV infection by the broadly cross-reactive E1-specific MAb 1A4B-6. 1A4B-6 protected 3-week-old Swiss Webster mice prophylactically from lethal VEEV challenge. Likewise, 1A4B-6 inhibited virus growth in vitro at a pre-attachm...
The Structural Biology of Eastern Equine Encephalitis Virus, an Emerging Viral Threat. Alphaviruses are arboviruses that cause arthritis and encephalitis in humans. Eastern Equine Encephalitis Virus (EEEV) is a mosquito-transmitted alphavirus that is implicated in severe encephalitis in humans with high mortality. However, limited insights are available into the fundamental biology of EEEV and residue-level details of its interactions with host proteins. In recent years, outbreaks of EEEV have been reported mainly in the United States, raising concerns about public safety. This review article summarizes recent advances in the structural biology of EEEV based mainly on single-par...
Structure and Sequence Requirements for RNA Capping at the Venezuelan Equine Encephalitis Virus RNA 5′ End. Venezuelan equine encephalitis virus (VEEV) is a reemerging arthropod-borne virus causing encephalitis in humans and domesticated animals. VEEV possesses a positive single-stranded RNA genome capped at its 5' end. The capping process is performed by the nonstructural protein nsP1, which bears methyl and guanylyltransferase activities. The capping reaction starts with the methylation of GTP. The generated mGTP is complexed to the enzyme to form an mGMP-nsP1 covalent intermediate. The mGMP is then transferred onto the 5'-diphosphate end of the viral RNA. Here, we explore the specificities of the...
Seroprevalence of arboviruses in Ecuador: Implications for improved surveillance. Arthropod-borne viruses (arboviruses) cause morbidity and mortality in humans and domestic animals worldwide. The percentage of population immunity or susceptibility to these viruses in Ecuador is unknown. To investigate the proportion of Ecuadorian populations with IgG antibodies (Abs) (past exposure/immunity) and IgM Abs (current exposure) against flaviviruses and alphaviruses and to study the activity of these viruses in Ecuador. During 2009-2011, we conducted a serosurvey for selected arboviruses in humans (n=1,842), equines (n=149), and sentinel hamsters (n=84) at two coastal locations an...
Serological evidence of Eastern equine encephalitis circulation in equids in Pará state, Brazil. Serum samples from 89 equids were analyzed (75 horses, 9 donkeys, and 5 mules) from the municipality of Viseu, Pará state, Brazil. Samples were collected in November 2014 and August 2015. The antibody prevalence against the following alphaviruses was estimated: Eastern equine encephalitis virus, Western equine encephalitis virus, Mucambo virus, and Mayaro virus. Seroprevalence was determined by the hemagglutination inhibition (HI) technique. Sera that exhibited HI antibodies with heterotypic reactions for the analyzed viruses were subjected to the 90% plaque reduction neutralization test (PRN...
Sindbis virus neutralising antibodies detected in Swedish horses. A number of viruses transmitted by mosquitoes are well known to cause disease in both humans and horses, ranging from mild fevers to mortal neurological disease. A recently discovered connection between the alphavirus Sindbis virus (SINV) and neurological disease in horses in South Africa initiated this serological study in northern Europe, where the same genotype of SINV (SINV-I) is also highly endemic. We tested 171 serum samples, originally obtained from horses for other reasons from April to October 2019, for presence of SINV neutralising antibodies using a plaque reduction neutralisation ...
Arbovirus serosurvey (Orthobunyavirus, Flavivirus, and Alphavirus) in a draft horse population from Santa Fe, Argentina (2013-2016). In the present study, we serosurveyed the exposure of 222 draft horses to different arboviruses in the city of Santa Fe, Argentina. Plaque reduction neutralization tests confirmed exposure to Fort Sherman virus (FSV), Saint Louis encephalitis virus (SLEV), West Nile virus (WNV), and Río Negro virus (RNV). Apparently, Western and Eastern equine encephalitis viruses did not circulate in the population tested. The confirmation of five seroconversions for WNV, FSV, and SLEV and the association between prevalence and age are indicative of recent circulation. These results highlight the importance ...
Rationally Attenuated Vaccines for Venezuelan Equine Encephalitis Protect Against Epidemic Strains with a Single Dose. Venezuelan equine encephalitis virus (VEEV) is a re-emerging virus of human, agriculture, and bioweapon threat importance. No FDA-approved treatment is available to combat Venezuelan equine encephalitis in humans, prompting the need to create a vaccine that is safe, efficacious, and cannot be replicated in the mosquito vector. Here we describe the use of a serotype ID VEEV (ZPC-738) vaccine with an internal ribosome entry site (IRES) to alter gene expression patterns. This ZPC/IRES vaccine was genetically engineered in two ways based on the position of the IRES insertion to create a vaccine th...
Clinical and Serological Findings of Madariaga and Venezuelan Equine Encephalitis Viral Infections: A Follow-up Study 5 Years After an Outbreak in Panama. Human cases of Madariaga virus (MADV) infection were first detected during an outbreak in 2010 in eastern Panama, where Venezuelan equine encephalitis virus (VEEV) also circulates. Little is known about the long-term consequences of either alphavirus infection. Methods: A follow-up study of the 2010 outbreak was undertaken in 2015. An additional survey was carried out 2 weeks after a separate 2017 alphavirus outbreak in a neighboring population in eastern Panama. Serological studies and statistical analyses were undertaken in both populations. Results: Among the originally alphavirus-seronegat...
Comparative pathology study of Venezuelan, eastern, and western equine encephalitis viruses in non-human primates. Venezuelan, eastern, and western equine encephalitis viruses (VEEV, EEEV, and WEEV) are mosquito-borne viruses in the Americas that cause central nervous system (CNS) disease in humans and equids. In this study, we directly characterized the pathogenesis of VEEV, EEEV, and WEEV in cynomolgus macaques following subcutaneous exposure because this route more closely mimics natural infection via mosquito transmission or by an accidental needle stick. Our results highlight how EEEV is significantly more pathogenic compared to VEEV similarly to what is observed in humans. Interestingly, EEEV appears...
Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis. Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus e...
National Seroprevalence and Risk Factors for Eastern Equine Encephalitis and Venezuelan Equine Encephalitis in Costa Rica. Eastern equine encephalitis and Venezuelan equine encephalitis are endemic neglected tropical diseases in the Americas, causing encephalitis in both horses and humans. In 2013, a cross-sectional study was performed in 243 horses located in the highlands and lowlands throughout Costa Rica. Serum samples were analyzed with an IgG ELISA and confirmed by the plaque-reduction neutralization test (PRNT80). Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) overall seroprevalences by the PRNT80 were 36% (95% confidence interval [CI]: 29.9-42.5; 78/217 horses) and...
Ross River Virus Infection of Horses: Appraisal of Ecological and Clinical Consequences. Ross River virus (RRV) is a mosquito-borne arbovirus of the genus Alphavirus that causes disease in humans and horses in Australia. A temporal association of RRV infection in horses with clinical signs including pyrexia, malaise, and polyarthralgia has been reported, along with reduced athletic performance, often for extended periods. Despite these reports, disease due to RRV remains somewhat controversial as experimental infection of horses has resulted in obvious viraemia yet minimal signs of clinical disease. The relatively high viraemia demonstrated by horses infected with RRV has led to s...
Zoonotic Alphaviruses in Fatal and Neurologic Infections in Wildlife and Nonequine Domestic Animals, South Africa. Alphaviruses from Africa, such as Middelburg virus (MIDV), and Sindbis virus (SINV), were detected in horses with neurologic disease in South Africa, but their host ranges remain unknown. We investigated the contribution of alphaviruses to neurologic infections and death in wildlife and domestic animals in this country. During 2010-2018, a total of 608 clinical samples from wildlife and nonequine domestic animals that had febrile, neurologic signs or unexplained deaths were tested for alphaviruses. We identified 32 (5.5%) of 608 alphavirus infections (9 SINV and 23 MIDV), mostly in neurotissue...
Impact of the Southern Oscillation Index, Temperature, and Precipitation on Eastern Equine Encephalitis Virus Activity in Florida. Eastern equine encephalitis virus (EEEV), an Alphavirus from family Togaviridae, is a highly pathogenic arbovirus affecting the eastern United States, especially Florida. Effects of the Southern Oscillation Index (SOI), precipitation, and cooling degree days on EEEV horse case data in Florida from 2004 to 2018 were modeled using distributed lag nonlinear models (DLNMs). The analysis was conducted at statewide and regional scales. DLNMs were used to model potential delayed effects of the covariates on monthly counts of horse cases. Both models confirmed a seasonal trend in EEEV transmission and...
Molecular and cellular evidence of natural Venezuelan equine encephalitis virus infection in frugivorous bats in Colombia. Venezuelan equine encephalitis virus (VEEV) is an alphavirus that causes encephalitis with a high impact on public health in Latin America. However, only in Guatemala, Trinidad and Tobago, and Mexico have found antibodies in VEEV in bats, using immunohistochemistry, the sensitivity and specificity are improved; thus, it is better for demonstrating natural infection in bats as potential hosts. This study aimed to determine the presence of VEEV in tissues of frugivorous bats. Methods: A prospective descriptive cross-sectional study with a non-probabilistic sampling was carried out in 12 localiti...
Conformational plasticity of the VEEV macro domain is important for binding of ADP-ribose. Venezuelan equine encephalitis virus (VEEV) is a new world alphavirus which can be involved in several central nervous system disorders such as encephalitis and meningitis. The VEEV genome codes for 4 non-structural proteins (nsP), of which nsP3 contains a Macro domain. Macro domains (MD) can be found as stand-alone proteins or embedded within larger proteins in viruses, bacteria and eukaryotes. Their most common feature is the binding of ADP-ribose (ADPr), while several macro domains act as ribosylation writers, erasers or readers. Alphavirus MD erase ribosylation but their precise contributi...
Human cathelicidin peptide LL-37 as a therapeutic antiviral targeting Venezuelan equine encephalitis virus infections. Venezuelan equine encephalitis virus (VEEV), a new world alphavirus belonging to the Togaviridae family, causes periodic disease outbreaks in humans and equines with high associated mortality and morbidity. VEEV is highly infectious via the aerosol route and so has been developed as a biological weapon (Hawley and Eitzen, 2001). Despite its current classification as a category B select agent, there are no FDA approved vaccines or therapeutics to counter VEEV infections. Here we utilize a naturally occurring host defense peptide, LL-37, as a therapeutic strategy to inhibit VEEV multiplication i...
Venezuelan Equine Encephalitis Virus Capsid Implicated in Infection-Induced Cell Cycle Delay in vitro. Venezuelan equine encephalitis virus (VEEV) is a positive sense, single-stranded RNA virus and member of the New World alphaviruses. It causes a biphasic febrile illness that can be accompanied by central nervous system involvement and moderate morbidity in humans and severe mortality in equines. The virus has a history of weaponization, lacks FDA-approved therapeutics and vaccines in humans, and is considered a select agent. Like other RNA viruses, VEEV replicates in the cytoplasm of infected cells and eventually induces apoptosis. The capsid protein, which contains a nuclear localization and...
Seroprevalence and associated risk factors of mosquito-borne alphaviruses in horses in northern Queensland. To investigate the seroprevalence and associated risk factors of alphaviruses (Ross River virus (RRV), Barmah Forest virus (BFV) and Whataroa virus (WHAV)) in northern Queensland horses. Methods: A cross-sectional study of alphavirus antibodies in horses (n = 287) from 147 properties in northern Queensland from September 2013 to June 2014 was conducted. Owners of sampled horses were interviewed on potential risk factors. Data were analysed for associations using multivariable logistic regression. Results: Antibody titres for RRV were demonstrated in samples from 134 properties (91%; 95% co...
