The study of viral infections that affect equine species assesses the relationship between viruses and horses. Infections can lead to a range of clinical symptoms and may impact the health and performance of horses. Common equine viruses include Equine Influenza Virus, Equine Herpesvirus, and West Nile Virus, among others. Understanding the mechanisms of viral transmission, pathogenesis, and host immune responses is essential for developing effective prevention and treatment strategies. This page compiles peer-reviewed research studies and scholarly articles that explore the epidemiology, molecular biology, and clinical management of viral infections in horses.
Cornelisse K, Ionescu AM.Keesjan Cornelisse and Andra-Maria Ionescu discuss the clinical presentation, investigation and diagnostic approach to a case of orthoflavivirus infection in a horse in south-west England.
Leo LK, Bergvall KE.Equine aural plaque caused by equine papilloma viruses is common worldwide and affected horses can show severe clinical signs. Due to its viral aetiology, in some countries affected horses are not allowed to compete. Since lesions persist, showing no spontaneous regression, effective and safe treatment is required. Currently, the only treatment with consistent efficacy is imiquimod. Treatment time is prolonged and adverse effects are common. In humans, papilloma warts are successfully and safely treated with topical nitric-zinc complex solutions inducing a painless caustic effect. Objective: T...
Veit M, Matczuk AK.Equine arteritis virus (EAV) is a positive-stranded RNA virus of the Arteriviridae family. Its GP5/M dimer, the principal component of the viral envelope, mediates virus budding and serves as a key target for neutralizing antibodies. Using AlphaFold3, we predicted the 3D structure of the EAV GP5/M dimer and compared it to its homolog in porcine reproductive and respiratory syndrome virus (PRRSV). Both complexes share a conserved architecture comprising a short ectodomain, three helical transmembrane regions, and a β-sheet-rich endodomain. EAV GP5 features a longer ectodomain with four α-heli...
Whitlock F, Grewar J, Newton R.The epidemiology of equine influenza (EI) in the United Kingdom has not been systematically described since the 2019 epidemic. Objective: To summarise UK EI surveillance (2020-2024), quantify outbreak seasonality and assess movement-related sources. Methods: Retrospective observational analysis of national surveillance and horse importation data. Methods: Epidemiological data for laboratory-confirmed EI cases in the United Kingdom were collated. Outbreaks (EI-infected premises) were defined as one or more laboratory-confirmed cases on the same premises within a 4-week period. Monthly outbreak ...
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...
Acevedo-Jiménez GE, Morales-González C, Akbarin MM, Rodríguez-Murillo C, González-Fernández VD, Avila-De la Vega LM, García-Flores MM....Equine infectious anemia virus (EIAV) is a globally significant equine pathogen, and its control relies on effective serological surveillance. The agar gel immunodiffusion (AGID) test, the WOAH-prescribed method, has limitations in sensitivity. This study developed and validated an indirect ELISA using a synthetic peptide derived from a conserved region of the EIAV gp90 surface glycoprotein. The assay was evaluated using 773 horse sera from the Metropolitan Zone of the Valley of Mexico and compared to the AGID test. The gp90-EIAV ELISA demonstrated a sensitivity of 85.3 % and a specificity o...
Zanacchi A, Fruscione F, Grasselli S, Razzuoli E, Pastorino L, Di Lisa D.Developing advanced preclinical in vitro cancer models is essential for understanding tumor biology, improving drug discovery, and enhancing the clinical translation of new therapies. Papillomaviruses (PVs) cause diverse lesions in humans and animals; notably, bovine papillomavirus (BPV) is the main cause of equine sarcoid, the most common skin tumor in horses. Its pathogenesis involves viral infection, fibroblast transformation, and extracellular matrix (ECM) remodeling. These processes highlight the limitations of conventional two-dimensional (2D) culture systems, which fail to replicate the...
Penzhorn L, Crafford JE, Guthrie AJ.African horse sickness (AHS) is the only equine disease for which the World Organisation for Animal Health (WOAH) gives official disease-free status, given that it poses a major threat to the equine industry. The disease is caused by AHS virus (AHSV; family , taxon species ), which is endemic in sub-Saharan Africa. Reverse-transcription quantitative real-time PCR (RT-qPCR) is a rapid, sensitive detection method used in the diagnosis of AHS and the certification of animals as negative for AHSV for the purpose of movement. Genetic variability of AHSV may influence the accuracy of RT-qPCR detecti...
Mkpuma N, Meseko C, Shittu I, Chukwu C, Afiukwa FN, Iroha IR, Muhammad M, Ogbu O.Equine influenza virus (EIV) H3N8 is a highly contagious respiratory pathogen that poses significant health and economic risks to equids globally. In southeastern Nigeria where equids are sold and slaughtered, limited data exist on EIV epidemiology and circulating lineages. Methods: To address this gap, an active surveillance was conducted between January 2022 and October 2023. A total of 400 nasal swabs were collected from horses and donkeys at slaughterhouses and animal markets. The swabs were screened for equine influenza virus (EIV) using quantitative Reverse-Transcription Polymerase Chain...
Li Z, Yu T, Ge L, Lv S, Fu Q, Shi H.Equine herpesvirus type 1 (EHV-1) is a major veterinary pathogen causing significant economic losses in the livestock industry. Despite its impact, effective vaccines and targeted antiviral strategies remain limited, largely due to an incomplete understanding of host factors regulating viral replication and pathogenesis. Unassigned: To systematically identify host genes essential for EHV-1 infection, we established a BHK-21 cell line stably expressing Cas9 and performed a genome-wide CRISPR/Cas9 knockout screen using a pooled lentiviral single-guide RNA library. Significantly enriched candidat...
Schmitz M, Neugebauer E, Full F, Conn KL.Comparative transcriptomics offers a powerful approach to elucidate host-virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species' cells infected with three alphaherpesviruses-herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)-to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection...
Schliewert EC, Hooijberg EH, Goddard A.African horse sickness (AHS), caused by the vector-borne African horse sickness virus (AHSV), is endemic to sub-Saharan Africa and infection results in high mortality in naïve equine populations. Clinical signs include submucosal petechiae and prolonged bleeding post venepuncture indicative of hypocoagulation. Pathological activation of haemostasis may result from tissue factor expression as a result of vascular endothelial damage or dysfunction, the proposed pathologic mechanism in AHS, potentially resulting in disseminated intravascular coagulation (DIC). Objective: To describe haemostatic ...
Thieulent CJ, Sarkar S, Carossino M, Bhowmik M, Zhu H, Balasuriya UBR.Our laboratory identified the susceptible allelic variant of equine CXCL16 protein (EqCXCL16S) as an entry receptor for equine arteritis virus (EAV). However, EAV has a broad host cell tropism and infects cells that lack EqCXCL16S. Thus, we hypothesized that EAV interacts with other host cell protein(s) that facilitate EAV infection. A virus overlay protein-binding assay in combination with a Far-Western blot from EAV-susceptible equine pulmonary artery endothelial cells (EECs) and equine dermal fibroblasts (E. Derm) identified a 57 kDa protein, present in the membrane fraction of the protein ...
Beniwal N, Lal B, Mithina S, Verma CK, Kumar S, Phagna V, Jakhar K, Sonar S, Gupta V, Singh R, Kumar N, Tan CW, Thachamvally R, Singha H, Murzello K....Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission ...
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...
Cooper CJ, Arroyo LG, Hammermueller JD, Botts MM, Pearl DL, Wootton SK, Lillie BN.Equine herpesvirus-1 (EHV-1) is ubiquitous in the horse population, but prevalence estimates have ranged from 3 to 88% depending on the population and method of sampling. No prevalence studies have been carried out in Ontario, Canada. The objective of this study was to measure the prevalence of EHV-1 shedding in healthy broodmares in Ontario. A total of 381 mares from 42 farms in Ontario were sampled, including pregnant and barren broodmares. Samples were collected from the nose, vagina, and blood of each mare up to 6 times from December 2016 through October 2017 using a cross-sectional study ...
Jager MC, Luethy D, Shallop S, Cathcart J, Divers TJ, Tan JY, Beasley EM, Johnson P, Leduc L, Smith C, Jamieson CA, Magdesian KG, Van de Walle GR....Equine hepacivirus (EqHV) is closely related to hepatitis C virus (HCV), which causes persistent infection and chronic hepatitis in people. Information on persistent EqHV infection and hepatitis is limited. Objective: To report 19 cases of chronic hepatitis and persistent EqHV infection. Methods: Mixed retrospective and prospective case series. Methods: Inclusion criteria were: (1) chronic hepatitis, defined as persistently increased serum liver biomarkers, increased serum liver biomarkers accompanied by histopathological evidence of chronicity, for example, fibrosis, or both; (2) positive ser...
Ketphan W, Sato M, Tsujimura K, Mizutani T, Takemae H.Equine rhinitis B virus (ERBV), a member of the Picornaviridae family, is associated with mild to moderate respiratory illness in horses, yet its genomic diversity remains incompletely characterized. In this study, we performed metagenomic analysis on a rectal swab sample from a diarrheic foal confirmed to be positive for rotavirus A. Unexpectedly, we identified a highly divergent ERBV strain with a 9,448-nucleotide genome encoding a 2,721-amino-acid polyprotein. Sequence analysis revealed only 62.5-63.1% identity in the polyprotein and 47.1-49.8% in the VP1 region compared to known ERBV serot...
Pourmahdi Borujeni M, Ghobadian Diali H, Mashhadi AG, Aliabad MJ.The recent identification of novel viruses associated with hepatitis in horses has prompted equine veterinarians to investigate the viral factors contributing to equine hepatitis. Hepacivirus equi (EqHV), a member of the Flaviviridae family within the Hepacivirus genus, has been detected in horses affected by hepatitis. Globally, EqHV is highly conserved, existing as a single genotype with three distinct subtypes (Subtypes 1-3). Numerous studies have detected the virus by PCR and identified EqHV-specific antibodies through serological tests in different regions worldwide. However, to the best ...
Barua S, Tarannum A, Huber L, Easterwood LA, Velayudhan B, Da Silveira BP, Enyetornye B, Cohen ND, Dimitrov KM, Schwarz ER, Awtrey A, Groover E....Over the past decade, newly identified equine hepatotropic flavi- and parvoviruses, such as equine parvovirus-hepatitis (EqPV-H) and equine hepacivirus (EqHV), have generated considerable scientific and clinical interest. Pegiviruses, including Pegivirus (P.) caballi and P. equi, are also recognized and known to frequently cause persistent infections. However, comprehensive epidemiological data in the United States remain limited. This study analyzed 1195 equine serum samples collected from university-owned horses and diagnostic submissions across Alabama, Georgia, and Texas. Quantitative PCR ...
In 2017, Spain reported its first equine infectious anemia virus (EIAV) outbreak in 34 years, affecting three horses in two unrelated holdings in Candeleda (Ávila) and Serradilla (Cáceres), with no apparent epidemiological link between premises. Phylogenetic analysis of whole genome and the gene revealed that the Spanish EIAV strains form a distinct monophyletic clade, sharing more than 99% nucleotide identity, suggesting a common contamination event. Interestingly, these three viral strains seem to cluster with North American strains, sharing up to 80.12% nucleotide identity, notably with ...
Gonzálvez M, Franco JJ, Cano-Terriza D, Barbero-Moyano J, Jose-Cunilleras E, García J, Alguacil E, García-Bocanegra I.Equine Infectious Anemia (EIA) is a notifiable disease caused by Equine Infectious Anemia Virus (EIAV), with major sanitary and economic importance for equids worldwide. There is limited and outdated information on the circulation of EIAV in many European countries. In the present study, we aimed to assess virus exposure in different equid species in Western Europe. Methods: Between 2011 and 2023, a cross-sectional study was conducted to investigate the seroprevalence of EIAV in 1676 equids (1444 horses, 106 donkeys and 126 mules/hinnies) from four European regions: Andalusia (Southern Spain; ...
Bhat S, Karunakaran S, Frossard JP, Choudhury B, Steinbach F.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, a notifiable respiratory and reproductive disease of equids that causes significant losses to the equine industry. This study presents a comprehensive analysis of two EAV outbreaks in the UK in 2019, combining virus isolation, sequencing and phylogenetic analysis to provide a holistic understanding of EAV dynamics in these outbreaks. Genetic characterization revealed that all outbreak strains were similar to viruses detected in the UK and Europe from 2004 to 2011, belonging to phylogroup D and clustering in two grou...
Morales J, Ruano MJ, Tena-Tomás C, van Schalkwyk A, Loundras EA, Valero-Lorenzo M, López-Herranz A, Romito M, Batten C, Villalba R, Agüero M.African horse sickness (AHS) is a disease affecting equids caused by the AHS virus (AHSV). The World Organisation for Animal Health (WOAH) includes AHS as a notifiable disease and, upon detection within the European Union, immediate control and eradication measures are mandated. Thus, validated diagnostic methods for rapid AHSV detection are essential. The Agüero 2008 and Guthrie 2013 rRT-PCR methods have been widely validated for detection of any AHSV strain and are included as reference rRT-PCRs in the WOAH manual. However, the WOAH Reference Laboratory for AHS in the Republic of South Afri...
Conn KL.Equid alphaherpesvirus 1 (EHV1) is a DNA virus that causes severe disease in equids. Some strains are neurotropic and cause disease in the central nervous system, whereas others are non-neurotropic and can cause negative reproductive outcomes. Mechanisms governing EHV1 pathotype are not understood. However, EHV1 pathotypes have different infection efficiencies and replication kinetics in various cell types. They are also differentially susceptible to epigenetic inhibitors. Aside from this observation little is known about EHV1 chromatin or how its regulation influences infection. To build know...
White J, Thompson K, van den Berg D, O'Neill G, Mendez DH, Talwar J, Degeling C, Forsythe R, Durrheim DN.With more than 60% of emerging infectious diseases being zoonotic, we apply a One Health lens that connects human, animal, and environmental dimensions of the response to a Hendra virus (HeV) event. One Health promotes collaboration among health professionals, veterinarians, environmental scientists, and policymakers to strengthen health infrastructure and improve responses to complex health threats. HeV is an uncommon high-consequence and potentially fatal zoonotic disease endemic to parts of Australia. Previous research has largely focused on the uptake of preparedness measures by veterinari...
Haywood LMB, Clark A, Hause B, Sheahan B.Many cases of equine enterocolitis are suspected to be infectious in nature, but no pathogen is identified in many cases. Objective: Perform next-generation sequencing on faeces collected from cases of equine enterocolitis for the presence of novel viruses and determine if an identified novel virus is associated with cases of equine enterocolitis. Methods: Retrospective cohort study. Methods: Next generation sequencing was performed targeting viral genomes from n = 13 pooled faecal samples (n = 5 horses/pool) with enterocolitis. Subsequent qPCR was performed targeting the highly conser...
This study presents the first investigation of West Nile virus (WNV) seroprevalence among farmed horses in Kazakhstan. In 2024, a total of 368 serum samples were collected from horses across 106 settlements in 10 regions of the Republic of Kazakhstan. Using an enzyme-linked immunosorbent assay (ELISA), antibodies to WNV were detected in 32 horses (8.7%; 95% CI: 6.2-12.0%) from six regions. Among the seropositive animals, 26 (81.25%) were females and 6 (18.75%) were males, ranging in age from 1 to 19 years. No statistically significant association between sex and the presence of antibodies to W...
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...
Connor RJ, Kawaoka Y, Webster RG, Paulson JC.The receptor specificity of 56 H2 and H3 influenza virus isolates from various animal species has been determined to test the relevance of receptor specificity to the ecology of influenza virus. The results show that the receptor specificity of both H2 and H3 isolates evaluated for sialic acid linkage specificity and inhibition of hemagglutination by horse serum correlates with the species of origin, as postulated earlier for H3 strains based on a limited survey of five human, three avian, and one equine strain. Elucidation of the amino acid sequence of several human H2 receptor variants and a...
Murray K, Selleck P, Hooper P, Hyatt A, Gould A, Gleeson L, Westbury H, Hiley L, Selvey L, Rodwell B.A morbillivirus has been isolated and added to an increasing list of emerging viral diseases. This virus caused an outbreak of fatal respiratory disease in horses and humans. Genetic analyses show it to be only distantly related to the classic morbilliviruses rinderpest, measles, and canine distemper. When seen by electron microscopy, viruses had 10- and 18-nanometer surface projections that gave them a "double-fringed" appearance. The virus induced syncytia that developed in the endothelium of blood vessels, particularly the lungs.
Suzuki Y, Ito T, Suzuki T, Holland RE, Chambers TM, Kiso M, Ishida H, Kawaoka Y.The distribution of sialic acid (SA) species varies among animal species, but the biological role of this variation is largely unknown. Influenza viruses differ in their ability to recognize SA-galactose (Gal) linkages, depending on the animal hosts from which they are isolated. For example, human viruses preferentially recognize SA linked to Gal by the alpha2,6(SAalpha2,6Gal) linkage, while equine viruses favor SAalpha2,3Gal. However, whether a difference in relative abundance of specific SA species (N-acetylneuraminic acid [NeuAc] and N-glycolylneuraminic acid [NeuGc]) among different animal...
den Boon JA, Snijder EJ, Chirnside ED, de Vries AA, Horzinek MC, Spaan WJ.The nucleotide sequence of the genome of equine arteritis virus (EAV) was determined from a set of overlapping cDNA clones and was found to contain eight open reading frames (ORFs). ORFs 2 through 7 are expressed from six 3'-coterminal subgenomic mRNAs, which are transcribed from the 3'-terminal quarter of the viral genome. A number of these ORFs are predicted to encode structural EAV proteins. The organization and expression of the 3' part of the EAV genome are remarkably similar to those of coronaviruses and toroviruses. The 5'-terminal three-quarters of the genome contain the putative EAV p...
Plowright RK, Foley P, Field HE, Dobson AP, Foley JE, Eby P, Daszak P.Anthropogenic environmental change is often implicated in the emergence of new zoonoses from wildlife; however, there is little mechanistic understanding of these causal links. Here, we examine the transmission dynamics of an emerging zoonotic paramyxovirus, Hendra virus (HeV), in its endemic host, Australian Pteropus bats (fruit bats or flying foxes). HeV is a biosecurity level 4 (BSL-4) pathogen, with a high case-fatality rate in humans and horses. With models parametrized from field and laboratory data, we explore a set of probable contributory mechanisms that explain the spatial and tempor...
Quinlivan M, Zamarin D, García-Sastre A, Cullinane A, Chambers T, Palese P.Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, w...
Selvey LA, Wells RM, McCormack JG, Ansford AJ, Murray K, Rogers RJ, Lavercombe PS, Selleck P, Sheridan JW.To describe the clinical and epidemiological features of an outbreak of a viral infection affecting humans and horses. Methods: Stables in Hendra, a suburb of Brisbane. Methods: Affected horses and humans, and at-risk human contacts. Results: A pregnant mare died two days after arrival from a paddock elsewhere in Brisbane. Eight to 11 days later, illness (depression, anorexia, fever, dyspnoea, ataxia, tachycardia, tachypnoea and nasal discharge) was reported among 17 other horses from the same or an adjoining stable. Fourteen horses died or were put down. Five and six days after the index mare...
Ching PK, de los Reyes VC, Sucaldito MN, Tayag E, Columna-Vingno AB, Malbas FF, Bolo GC, Sejvar JJ, Eagles D, Playford G, Dueger E, Kaku Y....During 2014, henipavirus infection caused severe illness among humans and horses in southern Philippines; fatality rates among humans were high. Horse-to-human and human-to-human transmission occurred. The most likely source of horse infection was fruit bats. Ongoing surveillance is needed for rapid diagnosis, risk factor investigation, control measure implementation, and further virus characterization.
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 ...
Pawelek KA, Huynh GT, Quinlivan M, Cullinane A, Rong L, Perelson AS.Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and ...
Puffer BA, Parent LJ, Wills JW, Montelaro RC.We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences con...
Burbelo PD, Dubovi EJ, Simmonds P, Medina JL, Henriquez JA, Mishra N, Wagner J, Tokarz R, Cullen JM, Iadarola MJ, Rice CM, Lipkin WI, Kapoor A.Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest p...
Weaver SC, Salas R, Rico-Hesse R, Ludwig GV, Oberste MS, Boshell J, Tesh RB.Venezuelan equine encephalomyelitis (VEE) virus has caused periodic epidemics among human beings and equines in Latin America from the 1920s to the early 1970s. The first major outbreak since 1973 occurred in Venezuela and Colombia during 1995, and involved an estimated 75,000 to 100,000 people. We report an epidemiological and virological investigation of this epidemic. Methods: Virus isolates were made in cell culture from human serum, human throat swabs, and brain tissue from aborted and stillborn human fetuses, as well as from horse brain tissue and pooled mosquito collections. Human sera ...
Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ.A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial e...
MacDonald GH, Johnston RE.The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which mi...
Saenz RA, Quinlivan M, Elton D, Macrae S, Blunden AS, Mumford JA, Daly JM, Digard P, Cullinane A, Grenfell BT, McCauley JW, Wood JL, Gog JR.A key question in pandemic influenza is the relative roles of innate immunity and target cell depletion in limiting primary infection and modulating pathology. Here, we model these interactions using detailed data from equine influenza virus infection, combining viral and immune (type I interferon) kinetics with estimates of cell depletion. The resulting dynamics indicate a powerful role for innate immunity in controlling the rapid peak in virus shedding. As a corollary, cells are much less depleted than suggested by a model of human influenza based only on virus-shedding data. We then explore...
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...
Williamson MM, Hooper PT, Selleck PW, Gleeson LJ, Daniels PW, Westbury HA, Murray PK.To determine the infectivity and transmissibility of Hendra virus (HeV). Methods: A disease transmission study using fruit bats, horses and cats. Methods: Eight grey-headed fruit bats (Pteropus poliocephalus) were inoculated and housed in contact with three uninfected bats and two uninfected horses. In a second experiment, four horses were inoculated by subcutaneous injection and intranasal inoculation and housed in contact with three uninfected horses and six uninfected cats. In a third experiment, 12 cats were inoculated and housed in contact with three uninfected horses. Two surviving horse...
van Dinten LC, den Boon JA, Wassenaar AL, Spaan WJ, Snijder EJ.Equine arteritis virus (EAV) is a positive-strand RNA virus that uses a discontinuous transcription mechanism to generate a nested set of six subgenomic mRNAs from which its structural genes are expressed. A stable bacterial plasmid (pEAV030) containing a full-length cDNA copy of the 12.7-kb EAV genome was constructed. After removal of a single point mutation in the replicase gene, RNA transcripts generated in vitro from pEAV030 were shown to be infectious upon electroporation into BHK-21 cells. A genetic marker mutation was introduced at the cDNA level and recovered from the genome of the pro...
Maclachlan NJ, Guthrie AJ.Arthropod-transmitted viruses (Arboviruses) are important causes of disease in humans and animals, and it is proposed that climate change will increase the distribution and severity of arboviral diseases. Orbiviruses are the cause of important and apparently emerging arboviral diseases of livestock, including bluetongue virus (BTV), African horse sickness virus (AHSV), equine encephalosis virus (EEV), and epizootic hemorrhagic disease virus (EHDV) that are all transmitted by haematophagous Culicoides insects. Recent changes in the global distribution and nature of BTV infection have been espec...
Kinney RM, Johnson BJ, Welch JB, Tsuchiya KR, Trent DW.Nucleotide sequence analysis of cDNA clones covering the entire genomes of Trinidad donkey (TRD) Venezuelan equine encephalitis (VEE) virus and its vaccine derivative, TC-83, has revealed 11 differences between the genomes of TC-83 virus and its parent. One nucleotide substitution and a single nucleotide deletion occurred in the 5'- and 3'-noncoding regions of the TC-83 genome, respectively. The deduced amino acid sequences of the nonstructural polypeptides of the two viruses differed only in a conservative Ser(TRD) to Thr(TC-83) substitution in nonstructural protein (nsP) three at amino acid ...
de Vries AA, Chirnside ED, Horzinek MC, Rottier PJ.We have recently shown that the genome of equine arteritis virus (EAV) contains seven open reading frames (ORFs). We now present data on the structural proteins of EAV and the assignment of their respective genes. Virions are composed of a 14-kDa nucleocapsid protein (N) and three membrane proteins designated M, GS, and GL. M is an unglycosylated protein of 16 kDa, and GS and GL are N-glycosylated proteins of 25 and 30 to 42 kDa, respectively. The broad size distribution of GL results from heterogeneous N-acetyllactosamine addition since it is susceptible to digestion by endo-beta-galactosidas...
Wang LF, Yu M, Hansson E, Pritchard LI, Shiell B, Michalski WP, Eaton BT.An outbreak of acute respiratory disease in Hendra, a suburb of Brisbane, Australia, in September 1994 resulted in the deaths of 14 racing horses and a horse trainer. The causative agent was a new member of the family Paramyxoviridae. The virus was originally called Equine morbillivirus but was renamed Hendra virus (HeV) when molecular characterization highlighted differences between it and members of the genus Morbillivirus. Less than 5 years later, the closely related Nipah virus (NiV) emerged in Malaysia, spread rapidly through the pig population, and caused the deaths of over 100 people. W...
Pallister J, Middleton D, Wang LF, Klein R, Haining J, Robinson R, Yamada M, White J, Payne J, Feng YR, Chan YP, Broder CC.The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirror...
Nugent J, Birch-Machin I, Smith KC, Mumford JA, Swann Z, Newton JR, Bowden RJ, Allen GP, Davis-Poynter N.Equid herpesvirus 1 (EHV-1) can cause a wide spectrum of diseases ranging from inapparent respiratory infection to the induction of abortion and, in extreme cases, neurological disease resulting in paralysis and ultimately death. It has been suggested that distinct strains of EHV-1 that differ in pathogenic capacity circulate in the field. In order to investigate this hypothesis, it was necessary to identify genetic markers that allow subgroups of related strains to be identified. We have determined all of the genetic differences between a neuropathogenic strain (Ab4) and a nonneuropathogenic ...
van Kasteren PB, Bailey-Elkin BA, James TW, Ninaber DK, Beugeling C, Khajehpour M, Snijder EJ, Mark BL, Kikkert M.Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cell...
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...
