Pathogenesis in horses refers to the biological mechanisms that lead to the development and progression of diseases within equine species. This process involves a complex interaction between the horse's immune system, genetic predispositions, environmental factors, and infectious agents such as bacteria, viruses, or parasites. Understanding pathogenesis is essential for identifying how diseases manifest and progress in horses, which can inform diagnostic and therapeutic strategies. Research in this area often focuses on specific diseases, examining factors such as pathogen entry, immune response, tissue damage, and recovery processes. This page compiles peer-reviewed research studies and scholarly articles that explore the mechanisms, contributing factors, and implications of pathogenesis in equine health.
Henríquez C, Morán G, Carrasco C, Sarmiento J, Barría M, Folch H, Uberti B.It is accepted that T regulatory cells (Treg) control different types of immune responses. In connection with this role, we have recently described an important increase in CD4+, CD25, Foxp3+ lymphocytes in the airway system of horses coursing with an exacerbation of severe equine asthma (EA). To explore the potential role of this population in the resolution of EA inflammation, we used a murine experimental model in which airway neutrophilic inflammation, which is similar to that observed in EA, is induced in mice by continual exposure to Aspergillus fumigatus contaminated hay. This model has...
Zarski LM, High EA, Nelli RK, Bolin SR, Williams KJ, Hussey G.Equine herpesvirus 5 (EHV-5) infection is associated with pulmonary fibrosis in horses, but further studies on EHV-5 persistence in equine cells are needed to fully understand viral and host contributions to disease pathogenesis. Our aim was to develop a quantitative PCR (qPCR) assay to measure EHV-5 viral copy number in equine cell cultures, blood lymphocytes, and nasal swabs of horses. Furthermore, we used a recently developed equine primary respiratory cell culture system to study EHV-5 pathogenesis at the respiratory tract. PCR primers and a probe were designed to target gene E11 of the EH...
Zavoshti FR, Andrews FM.Equine gastric ulcer syndrome (EGUS) is an umbrella term used to describe ulcers in the nonglandular squamous and glandular mucosa, terminal esophagus, and proximal duodenum. Gastric ulcers in the squamous and glandular regions occur more often than esophageal or duodenal ulcers and likely have a different pathogenesis. At present, omeprazole is accepted globally as the best pharmacologic therapy for both regions of the stomach; however, the addition of coating agents and synthetic prostaglandins could add to its effectiveness in treatment of EGUS. Dietary and environmental management are nece...
Mekuria ZH, El-Hage C, Ficorilli NP, Washington EA, Gilkerson JR, Hartley CA.Equine herpesvirus 5 (EHV5) is a commonly detected gammaherpesvirus, which, along with the closely related EHV2, constitute the only two known percaviruses that infect horses. Apart from detection in horse populations worldwide and the recent publication of the whole genome, there is little known about the biology and pathogenesis of this virus, with many assumptions made by parallels with EHV2. The long-term survival of gammaherpesviruses within infected hosts involves the establishment and maintenance of latency in selected cell and tissues types, particularly lymphocytes. A latent gammaherp...
Cappelli K, Cook RF, Stefanetti V, Passamonti F, Autorino GL, Scicluna MT, Coletti M, Verini Supplizi A, Capomaccio S.Equine infectious anaemia virus (EIAV) is a lentivirus with an almost worldwide distribution that causes persistent infections in equids. Technical limitations have restricted genetic analysis of EIAV field isolates predominantly to gag sequences resulting in very little published information concerning the extent of inter-strain variation in pol, env and the three ancillary open reading frames (ORFs). Here, we describe the use of long-range PCR in conjunction with next-generation sequencing (NGS) for rapid molecular characterization of all viral ORFs and known transcription factor binding mot...
Pfaender S, Walter S, Grabski E, Todt D, Bruening J, Romero-Brey I, Gather T, Brown RJ, Hahn K, Puff C, Pfankuche VM, Hansmann F, Postel A, Becher P....Hepatitis C virus (HCV) displays a restricted host species tropism and only humans and chimpanzees are susceptible to infection. A robust immunocompetent animal model is still lacking, hampering mechanistic analysis of virus pathogenesis, immune control, and prophylactic vaccine development. The closest homolog of HCV is the equine nonprimate hepacivirus (NPHV), which shares similar features with HCV and thus represents an animal model to study hepacivirus infections in their natural hosts. We aimed to dissect equine immune responses after experimental NPHV infection and conducted challenge ex...
Stewart AS, Pratt-Phillips S, Gonzalez LM.All species, including horses, suffer from alterations that increase intestinal permeability. These alterations, also known as "leaky gut," may lead to severe disease as the normal intestinal barrier becomes compromised and can no longer protect against harmful luminal contents including microbial toxins and pathogens. Leaky gut results from a variety of conditions including physical stressors, decreased blood flow to the intestine, inflammatory disease, and pathogenic infections, among others. Several testing methods exist to diagnose these alterations in both a clinical and research setting....
Mesquita LP, Arévalo AF, Zanatto DA, Miyashiro SI, Cunha EMS, de Souza MDCC, Villalobos EMC, Mori CMC, Maiorka PC, Mori E.The equine herpesvirus type 1 (EHV-1) is an important cause of myeloencephalopathy and respiratory disease in horses. Animal models for EHV-1 infection have been specially developed using mice and Syrian hamsters (Mesocricetus auratus). However, few studies have attempted to evaluate the pathogenesis of EHV-1 infection in the central nervous system (CNS) and respiratory system of hamsters. Therefore, the aim of this study was to evaluate the pathogenesis of four Brazilian EHV-1 strains within the CNS and lungs of Syrian hamsters. Hamsters intranasally infected with A4/72, A9/92, A3/97, and Iso...
Pawlina K, Gurgul A, Szmatoła T, Koch C, Mählmann K, Witkowski M, Bugno-Poniewierska M.Equine sarcoids are the most common neoplasms occurring in horses. Despite frequent occurrence, they are still not well described at the molecular level. Thus, in the present study, we performed a comprehensive comparative analysis of sarcoid miRNAome profile to identify aberrantly expressed microRNAs, along with their structural variants, potentially useful as biomarkers and, in a wider perspective, broaden the knowledge about this tumor and underlying mechanisms. To this end, we conducted next generation sequencing and as a result we identified both known and potentially novel miRNAs. Differ...
Zhao J, Poelaert KCK, Van Cleemput J, Nauwynck HJ.Equine herpesvirus type 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. Besides epithelial cells, CD172a monocytic cells become infected with EHV-1 in the respiratory mucosa and transport the virus from the apical side of the epithelium to the lamina propria en route to the lymph and blood circulation. Whether CD172a monocytic cells are specifically recruited to the infection sites in order to pick up virus is unknown. In our study, equine nasal mucosa explants were inoculated with EHV-1 neurological strains 03P37 and 95P105 or the non-neurological strains ...
Silva GTA, Guest BB, Gomez DE, McGregor M, Viel L, O'Sullivan ML, Runciman J, Arroyo LG.Calcification of the tunica media of the axial pulmonary arteries (PA) has been reported in a large proportion of racehorses. In humans, medial calcification is a significant cause of arterial stiffening and is implicated in the pathogenesis of cardiac, cerebral, and renal microvascular diseases. Pulse wave velocity (PWV) provides a measure of arterial stiffness. This study aimed to develop a technique to determine PA-PWV in horses and, secondarily, to investigate a potential association between PA-PWV and arterial fibro-calcification. A dual-pressure sensor catheter (PSC) was placed in the ma...
Koop G, Vrieling M, Storisteanu DM, Lok LS, Monie T, van Wigcheren G, Raisen C, Ba X, Gleadall N, Hadjirin N, Timmerman AJ, Wagenaar JA, Klunder HM....Bicomponent pore-forming leukocidins are a family of potent toxins secreted by Staphylococcus aureus, which target white blood cells preferentially and consist of an S- and an F-component. The S-component recognizes a receptor on the host cell, enabling high-affinity binding to the cell surface, after which the toxins form a pore that penetrates the cell lipid bilayer. Until now, six different leukocidins have been described, some of which are host and cell specific. Here, we identify and characterise a novel S. aureus leukocidin; LukPQ. LukPQ is encoded on a 45 kb prophage (ΦSaeq1) found i...
Grimm AL, Schoon HA, Schöniger S.Equine endometritis eosinophilica (EE) is rarely described and its diagnostic criteria are not defined. The aim of this study was to characterize histological features of EE. A data base (1995-2013) was searched for biopsies with increased eosinophils. This study included all biopsies with this diagnosis and representative biopsies without this record. The definition of equine EE was based on criteria for EE in women and the results of the determination of physiological numbers of eosinophils within the equine endometrium. EE was diagnosed in 55 mares. Biopsies of 10 mares contained eosinophil...
Negussie H, Gizaw D, Tesfaw L, Li Y, Oguma K, Sentsui H, Tessema TS, Nauwynck HJ.Infections with equine herpesviruses (EHVs) are widespread in equine populations worldwide. Whereas both EHV-1 and EHV-4 produce well-documented respiratory syndromes in equids, the contribution of EHV-2 and EHV-5 to disease of the respiratory tract is still enigmatic. This study describes the detection and genetic characterization of EHVs from equids with and without clinical respiratory disease. Virus-specific PCRs were used to detect EHV-1, -2, -4 and -5. From the total of 160 equids with respiratory disease, EHV-5 was detected at the highest prevalence (23.1%), followed by EHV-2 (20.0%), E...
Bian J, Khaychuk V, Angers RC, Fernández-Borges N, Vidal E, Meyerett-Reid C, Kim S, Calvi CL, Bartz JC, Hoover EA, Agrimi U, Richt JA, Castilla J....Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrP) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrP Although disease transmission to only a subset of infecte...
Cymerys J, Słońska A, Brzezicka J, Tucholska A, Chmielewska A, Rola J, Malik P, Bańbura MW.Equine herpesvirus type 1 (EHV-1) causes respiratory infections, abortion and neurological disorders in horses. Molecular epidemiology studies have demonstrated that a single-point mutation in DNA polymerase gene, resulting in an amino acid variation (N752/D752), is significantly associated with the neuropathogenic potential of EHV-1 strains. The aim of the study was to elucidate if there are any differences between neuropathogenic (EHV-1 26) and non-neuropathogenic (Jan-E and Rac-H) EHV-1 strains in their ability to infect neuronal cells. For the tested EHV-1 strains, cytopathic effect (CPE) ...
Goehring LS, Brandes K, Ashton LV, Wittenburg LA, Olea-Popelka FJ, Lunn DP, Soboll Hussey G.Equine herpesvirus-associated myeloencephalopathy is the result of endothelial cell infection of the spinal cord vasculature with equine herpesvirus-1 (EHV-1) during cell-associated viraemia. Endothelial cell infection requires contact between infected peripheral blood mononuclear and endothelial cells. Inflammation generated during viraemia likely upregulates adhesion molecule expression on both cell types increasing contact and facilitating endothelial cell infection. Objective: Evaluating the role of anti-inflammatory drugs in decreasing endothelial cell infection with EHV-1. Methods: In vi...
Schöniger S, Böttcher D, Theuß T, Schoon HA.Endometrial epithelial cells form a luminal barrier and are exposed to pathogens and non-infectious antigens. Toll-like receptors (TLRs) mediate pathogen defenses and tissue homeostasis, but are also involved in the pathogenesis of inflammatory and fibrosing alterations. Endometrial diseases are important causes of subfertility in mares. The pathogenesis of some types of persistent inflammation and periglandular fibrosis (endometrosis) is unknown. The aim of this study was to compare by in situ and in vitro immunohistochemistry the expression of TLRs 2, 4 and 6 in equine endometrial epithelial...
Frondoza CG, Fortuno LV, Grzanna MW, Ownby SL, Au AY, Rashmir-Raven AM.Objective Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA). Design Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) con...
Journal of proteomicsJanuary 3, 2017
Volume 154 102-108 doi: 10.1016/j.jprot.2016.12.015
Degroote RL, Uhl PB, Amann B, Krackhardt AM, Ueffing M, Hauck SM, Deeg CA.The membrane protein expression repertoire of cells changes in course of activation. In equine recurrent uveitis (ERU), a spontaneous autoimmune disease in horses with relapsing and ultimately blinding inner eye inflammation, CD4+ T lymphocytes are the crucial pathogenic cells activated in the periphery directly prior to an inflammatory episode. In order to find relevant changes in the membrane proteome associated to disease, we sorted CD4+ lymphocytes and compared protein abundance from the generated proteome datasets of both healthy horses and ERU cases. We detected formin like 1, a key play...
Arroyo LG, Costa MC, Guest BB, Plattner BL, Lillie BN, Weese JS.Duodenitis-proximal jejunitis (DPJ) is an acute sporadic gastrointestinal disorder of horses of unknown cause. Objective: We hypothesize that Clostridium difficile toxins are involved in the pathogenesis of DPJ in horses. The objective of this study was to determine whether experimentally delivered C. difficile toxins cause clinical signs and histologic lesions similar to those of naturally occurring DPJ. Methods: Six healthy mature mixed breed horses. Methods: Experimental study: animal model of animal disease. Fasted horses were administered crude C. difficile toxins via gastroscopy and moni...
Stokol T, Serpa PBS, Zahid MN, Brooks MB.Equid herpes virus type-1 (EHV-1) is a major pathogen of horses, causing abortion storms and outbreaks of herpes virus myeloencephalopathy. These clinical syndromes are partly attributed to ischemic injury from thrombosis in placental and spinal vessels. The mechanism of thrombosis in affected horses is unknown. We have previously shown that EHV-1 activates platelets through virus-associated tissue factor-initiated thrombin generation. Activated platelets participate in thrombus formation by providing a surface to localize coagulation factor complexes that amplify and propagate thrombin genera...
Laval K, Van Cleemput J, Poelaert KC, Brown IK, Nauwynck HJ.Equine herpesvirus type 1 (EHV-1) is responsible for respiratory disorders, abortion and myeloencephalopathy (EHM) in horses. Two pathotypes of EHV-1 strains are circulating in the field: neurovirulent (N) and non-neurovirulent (NN). For both strains, CD172a monocytic cells are one of the main carrier cells of EHV-1 during primary infection, allowing the virus to invade the horse's body. Recently, we showed that EHV-1 NN strains showed a restricted and delayed replication in CD172a cells. Here we characterize the in vitro replication kinetics of two EHV-1N strains in CD172a cells and investiga...
Yao Q, Ma J, Wang X, Guo M, Li Y, Wang X.Tetherin (BST-2) is an important host restriction factor that can inhibit the release of a diverse array of enveloped viruses from infected cells. Conversely, to facilitate their release and spread, many viruses have evolved various strategies to overcome the antiviral effect of tetherin in a species-specific manner. During the development of an attenuated equine infectious anemia virus (EIAV) vaccine in our laboratory, we found that serial passage of a field-isolated virulent EIAV strains in horse and donkey as well as the cultivated donkey cells, produces several typical EIAV strains, includ...
Leegwater PA, Vos-Loohuis M, Ducro BJ, Boegheim IJ, van Steenbeek FG, Nijman IJ, Monroe GR, Bastiaansen JW, Dibbits BW, van de Goor LH, Hellinga I....Inbreeding and population bottlenecks in the ancestry of Friesian horses has led to health issues such as dwarfism. The limbs of dwarfs are short and the ribs are protruding inwards at the costochondral junction, while the head and back appear normal. A striking feature of the condition is the flexor tendon laxity that leads to hyperextension of the fetlock joints. The growth plates of dwarfs display disorganized and thickened chondrocyte columns. The aim of this study was to identify the gene defect that causes the recessively inherited trait in Friesian horses to understand the disease proce...
Semik E, Gurgul A, Ząbek T, Ropka-Molik K, Koch C, Mählmann K, Bugno-Poniewierska M.Equine sarcoids are the most commonly detected skin tumours in Equidae. In the present research, a comparative transcriptomic analysis was performed which aimed at looking inside a tumour biology and identification of the expression profile as a potential source of cancer specific genes useful as biomarkers. We have used Horse Gene Expression Microarray data from matched equine sarcoids and tumour-distant skin samples. In total, 901 significantly differentially expressed genes (DEGs) between lesional and healthy skin samples have been identified (fold change ≥ 2; P < 0.05). The la...
Proft A, Spiesschaert B, Izume S, Taferner S, Lehmann MJ, Azab W.The serine-threonine protein kinase encoded by gene (pUS3) of alphaherpesviruses was shown to modulate actin reorganization, cell-to-cell spread, and virus egress in a number of virus species. However, the role of the US3 orthologues of equine herpesvirus type 1 and 4 (EHV-1 and EHV-4) has not yet been studied. Here, we show that is not essential for virus replication in vitro. However, growth rates and plaque diameters of a -deleted EHV-1 and a mutant in which the catalytic active site was destroyed were significantly reduced when compared with parental and revertant viruses or a virus in w...
Radakovic M, Davitkov D, Borozan S, Stojanovic S, Stevanovic J, Krstic V, Stanimirovic Z.The aim of this study was to determine the concentrations of oxidative stress parameters and DNA damage in horses infected by Theileria equi. Initial screening of 110 horses with duplex PCR enabled the selection of 30 infected horses with T. equi and 30 free of infection (control). Specimens from the 60 horses were further analysed by determining the following oxidative stress parameters: extent of haemolysis (EH), plasma free haemoglobin (PHb), catalase (CAT), Cu,Zn superoxide dismutase (SOD1), paraoxonase (PON1), nitrite (NO), total nitrate and nitrite (NOx), malondialdehyde (MDA) and free t...
Greppi MC, Guillot J, Melloul E, Bourdoiseau G, Lepage O, Cadoré JL.Guttural pouch mycosis (GPM) is a rare but potentially life-threatening condition in horses. GPM is caused by a fungal invasion into the mucosal lining of the guttural pouches and, frequently, the associated neurovascular structures. Although several species of fungi have been associated with this disease, Aspergillus spp. appear to be the most common isolated from the guttural pouches. However, it remains unclear which are the predisposing factors leading to the development of the infection. The objectives of the present study were to experimentally reproduce an infection by Aspergillus fumig...
Russell J, Matika O, Russell T, Reardon RJ.Osteochondrosis is considered multifactorial in origin, with factors such as nutrition, conformation, body size, trauma and genetics thought to contribute to its pathogenesis. Few studies have investigated the effects of genetic variability of osteochondrosis in Thoroughbreds. Objective: To describe the prevalence and genetic variability of a subset of osteochondrosis lesions in a group of Thoroughbred yearlings. Methods: Retrospective cohort study. Methods: Radiographs of 1962 Thoroughbred yearlings were retrieved from clinical records obtained between 2005 and 2013. Pedigree information was ...
Mayhew IG, deLahunta A, Whitlock RH, Geary JC.Five horses of mixed breeding and 1 zebra with symmetric tetraparesis and ataxia were studied. There were 2 females and 4 males. Signs of illness were first noticed from birth to 12 months of age. Clinical and pathologic studies were performed when the animals were 4 to 24 months old. Two of the horses were related. All of the subjects had diffuse degenerative myeloencephalopathy. The degeneration was most pronounced in thoracic segments of the spinal cord. Ventral and dorsolateral funiculi were most severely affected. Axonal swelling and abnormal neuronal cell bodies were seen in the gray mat...
Payne SL, Pei XF, Jia B, Fagerness A, Fuller FJ.The molecular clones pSPeiav19 and p19/wenv17 of equine infectious anemia virus (EIAV) differ in env and long terminal repeats (LTRs) and produce viruses (EIAV(19) and EIAV(17), respectively) of dramatically different virulence phenotypes. These constructs were used to generate a series of chimeric clones to test the individual contributions of LTR, surface (SU), and transmembrane (TM)/Rev regions to the disease potential of the highly virulent EIAV(17). The LTRs of EIAV(19) and EIAV(17) differ by 16 nucleotides in the transcriptional enhancer region. The two viruses differ by 30 amino acids i...
Peiffer RL, Wilcock BP, Yin H.Histologic examination was made of 1,419 globes from domestic animals (964 dogs, 374 cats, 41 horses, and 40 cattle) with ocular disease; pre-iridal membranes (rubeosis iridis) were found in 98. The membranes originated as endothelial budding from the anterior iridal stroma and seemed to mature into fibrous or fibrovascular membranes that were often followed by hyphema or, occasionally, glaucoma. Pre-existent disease in the 98 affected globes included chronic endophthalmitis (27/98), chronic glaucoma (24/98), anterior uveal melanoma (15/98), ciliary body adenoma (14/98), neoplasms metastatic t...
Art T, Kirschvink N, Smith N, Lekeux P.To test the hypothesis that reactive oxygen species could be associated to the lower airway disorders occurring in horses suffering from recurrent airway obstruction (RAO), indices of oxidative stress were studied in blood and pulmonary epithelium lining fluid in 5 RAO horses either in clinical remission or 24 h after the onset of a crisis of bronchospasm and in 5 healthy horses. Venous blood and bronchoalveolar lavage fluid (BALF) samples were collected and analysed for reduced glutathione (GSH), oxidised glutathione (GSSG), total glutathione (TGSH), glutathione redox ratio (GRR) in blood hae...
Berthoud H, Frey J, Kuhnert P.Actinobacillus equuli, a member of the family Pasteurellaceae is the etiologic agent of a frequently lethal septicemia in neonatal foals as well as other more chronic diseases like arthritis, pleuritis, pneumonia or peritonitis. It may also be isolated from the oral cavity of healthy horses. Hemolytic isolates of A. equuli are known but so far no virulence determinants have been described for this bacterial species. By screening hemolytic A. equuli strains with specific gene probes, a hemolysin, designated Aqx (A. equuli RTX (repeats in the structural toxin)) was identified. This hemolysin was...
van de Lest CH, Brama PA, van El B, DeGroot J, van Weeren PR.Osteochondrosis (OC) is the most important developmental orthopaedic disease in the horse. Despite some decades of research, much of the pathogenesis of the disorder remains obscure. Increasing knowledge of articular cartilage development in juvenile animals led to the presumption that the role of collagen in OC might be more important than previously thought. To study collagen characteristics of both cartilage and subchondral bone in young (5 and 11 months of age) horses, samples were taken of subchondral bone and articular cartilage from a group of 43 Dutch Warmblood foals and yearlings that...
Parma AE, Santisteban CG, Villalba JS, Bowden RA.Horses inoculated with either equine cornea or killed Leptospira interrogans serovars pomona, tarassovi, icterohaemorrhagiae, wolffi and hardjo, developed corneal opacity and produced antibodies which made it possible to demonstrate partial antigenic identity between equine cornea and four of those serovars employed. These antibodies were isolated by means of immunoadsorptions, purified by ion-exchange chromatography (DEAE-Sephadex A-50) and run by immuno-electrophoresis in agar gel. Both antibodies, anti-equine cornea and anti-leptospira, showed that they corresponded to the IgGb subclass. Th...
Aharonson-Raz K, Lohmann KL, Townsend HG, Marques F, Singh B.Heaves, an obstructive neutrophilic airway inflammation of horses, is triggered by dust components such as endotoxin and has similarities to human asthma. Pulmonary intravascular macrophages (PIMs) increase horses' sensitivity to endotoxin-induced lung inflammation; however, their role in an airborne pathology remains unknown. Therefore, we investigated the role of PIMs in the development of heaves in horses. Clinical and inflammatory responses were evaluated following induction of heaves by moldy hay exposure and PIM depletion with gadolinium chloride (GC). Mares (N = 9) were exposed to four ...
Bundgaard L, Åhrman E, Malmström J, Auf dem Keller U, Walters M, Jacobsen S.The objectives of this study was to establish a sensitive and reproducible method to map the cartilage and subchondral bone proteomes in quantitative terms, and mine the proteomes for proteins of particular interest in the pathogenesis of osteoarthritis (OA). The horse was used as a model animal. Protein was extracted from articular cartilage and subchondral bone samples from three horses in triplicate by pressure cycling technology or ultrasonication. Digested proteins were analysed by data independent acquisition based mass spectrometry. Data was processed using a pre-established spectral li...
Williams KJ, Robinson NE, Defeijter-Rupp H, Millerick-May M, Stack A, Hauptman J, Derksen FJ.Exercise-induced pulmonary hemorrhage (EIPH), which has been reported in humans and a variety of domestic animals following strenuous exercise, is most often documented in racehorses. Remodeling of pulmonary veins (VR) in equine EIPH was recently described, suggesting that it contributes to the pathogenesis of the disease. The cause of VR is unknown. We tested the hypothesis that the development of VR follows pulmonary blood flow distribution, preferentially occurring in the caudodorsal lung region. Furthermore, we hypothesized that VR underpins development of the other lesions of EIPH patholo...
de Grauw JC, Brama PA, Wiemer P, Brommer H, van de Lest CH, van Weeren PR.To assess whether reported alterations in metabolism of cartilage matrix in young (0 to 24 months old) horses with osteochondritis dissecans (OCD) may also be found in older (24 to 48 months old) horses with clinical signs of OCD and to investigate the role of eicosanoids in initiating these clinical signs. Methods: Synovial fluid was collected from 38 tarsocrural joints of 24 warmblood horses with (22 joints of 16 horses) or without (16 joints of 8 horses) clinical signs and a radiographic diagnosis of OCD of the distal intermediate ridge of the tibia. Methods: Turnover of type II collagen wa...
Trumble TN, Trotter GW, Oxford JR, McIlwraith CW, Cammarata S, Goodnight JL, Billinghurst RC, Frisbie DD.To determine concentrations of matrix metalloproteinase (MMP)-2 and -9 in synovial fluid; and mRNA expression of MMP-1, -13, and -3; interleukin[IL]-1alpha and beta; and tumor necrosis factor (TNF)-alpha in synovial membrane and articular cartilage from horses with naturally occurring joint disease. Methods: Synovial fluid (n = 76), synovial membrane (59), and articular cartilage (45) from 5 clinically normal horses and 55 horses with joint disease categorized as traumatic (acute [AT] or chronic [CT]), osteochondritis dissecans (OCD), or septic (S). Methods: Synovial fluid gelatinase concentra...
Kim SK, Kim S, Dai G, Zhang Y, Ahn BC, O'Callaghan DJ.The equine herpesvirus 1 (EHV-1) negative regulatory IR2 protein (IR2P), an early 1,165-amino acid (aa) truncated form of the 1487-aa immediate-early protein (IEP), lacks the trans-activation domain essential for IEP activation functions but retains domains for binding DNA, TFIIB, and TBP and the nuclear localization signal. IR2P mutants of the N-terminal region which lack either DNA-binding activity or TFIIB-binding activity were unable to down-regulate EHV-1 promoters. In EHV-1-infected cells expressing full-length IR2P, transcription and protein expression of viral regulatory IE, early EICP...
Marycz K, Michalak I, Kornicka K.Horses metabolic disorders have become an important problem of modern veterinary medicine. Pathological obesity, insulin resistance and predisposition toward laminitis are associated with Equine Metabolic Syndrome (EMS). Based on pathogenesis of EMS, dietary and cell therapy management may significantly reduce development of this disorder. Special attention has been paid to the diet supplementation with highly bioavailable minerals and mesenchymal stem cells (MSC) which increase insulin sensitivity. In nutrition, there is a great interests in natural algae enriched via biosorption process with...
May JP, Walker CA, Maskell DJ, Slater JD.Streptococcus equi subsp. equi is the causative agent of the equine disease strangles. In this study we describe the development of an in vivo Himar1 transposon system for the random mutagenesis of S. equi and, potentially, other Gram-positive bacteria. We demonstrate efficient and random transposition of a modified mini-transposon onto the chromosome by Southern blot analysis and insertion site sequencing. Non-haemolytic mutants were isolated at a frequency of 0.2%, and acapsular mutants at a frequency of 0.04%. Taken together, these data demonstrate that in vivo Himar1 mutagenesis can be use...
Franzén P, Berg AL, Aspan A, Gunnarsson A, Pringle J.A 19-year-old horse that was one of a group of six horses infected experimentally with Anaplasma phagocytophilum for a study of the pathogenesis of equine granulocytic ehrlichiosis died suddenly two days after first showing clinical signs of disease. The clinical signs and laboratory findings observed before its death were similar to all those of the other infected horses, and to previous reports of this disease. A postmortem examination revealed widespread haemorrhaging in its internal organs, and vasculitis and thrombosis in the kidneys. These changes are consistent with disseminated intrava...
Goehring LS, Soboll Hussey G, Gomez Diez M, Benedict K, Maxwell LK, Morley PS, Sloet van Oldruitenborgh-Oosterbaan MM, Lunn DP.Central nervous system blood vessel thrombosis is a part of the pathogenesis of equid herpesvirus-associated myeloencephalopathy (EHM). D-dimers (DD) are stable breakdown products of cross-linked fibrin, and increased DD-plasma concentrations could reflect the degree of systemic coagulation during EHV-1 infection. Objective: We hypothesized that blood DD concentrations will be increased during periods of EHV-1 fever and viremia, reflecting an activated coagulation cascade with fibrinolysis. Methods: Twenty-eight equids were infected with EHV-1 in 3 experimental infection studies. Three (uninfe...
Madigan JE, Haggettt EF, Pickles KJ, Conley A, Stanley S, Moeller B, Toth B, Aleman M.Increased plasma progestagen concentrations have been reported in foals with neonatal maladjustment syndrome (NMS). These steroids may cross the blood-brain barrier and have dampening effects in the central nervous system. Objective: To evaluate if the infusion of a progesterone derivative (allopregnanolone) in a healthy neonatal foal would induce clinical signs compatible with NMS. Methods: A healthy neonatal foal from a healthy mare with a normal gestation (length, no complications), birth and placenta was infused with allopregnanolone to observe its neurobehavioural effects. Heparinised blo...
Finlay M, Yuan Z, Morgan IM, Campo MS, Nasir L.Bovine papillomavirus type 1 infects not only cattle but also equids and is a causative factor in the pathogenesis of commonly occurring equine sarcoid tumours. Whilst treatment of sarcoids is notoriously difficult, cisplatin has been shown to be one of the most effective treatment strategies for sarcoids. In this study we show that in equine fibroblasts, BPV-1 sensitises cells to cisplatin-induced and UVB-induced apoptosis, a known cofactor for papillomavirus associated disease, however BPV-1 transformed fibroblasts show increased clonogenic survival, which may potentially limit the therapeut...
Yaniv A, Dahlberg J, Gazit A, Sherman L, Chiu IM, Tronick SR, Aaronson SA.Molecular clones of the integrated form of the genome of equine infectious anemia virus (EIAV), the etiologic agent of a naturally occurring, worldwide disease of horses, were obtained. The restriction map of a full-length genome was determined. Additional evidence for the close evolutionary relationship between EIAV and a prototype lentivirus (caprine arthritis encephalitis virus) was acquired by Southern blotting and immunological analyses. An interspecies radioimmunoassay was developed in which EIAV and ovine and caprine lentiviruses could be detected equally well. These studies make availa...
Lancaster WD, Theilen GH, Olson C.DNAs from bovine papilloma virus(BPV)-induced hamster tumors and from equine connective tissue tumors of unknown etiology were examined for BPV DNA sequences by molecular hybridization. DNA from two distinct classes of BPV (type 1 and type 2) was labeled in vitro and used as probes. Analysis of DNA-DNA reassociation kinetics indicated that both virus types were capable of tumor induction in the hamster. DNA isolated from 6 of 7 equine tumors accelerated the reassociation of the BPV DNA probes. BPV type 1 or type 2 DNA hybridized extensively to DNA from 3 tumors, while 3 other tumors contained ...
Shepard JJ, Andreadis TG, Thomas MC, Molaei G.Eastern equine encephalitis virus (EEEV) is a highly pathogenic mosquito-borne arbovirus, with active transmission foci in freshwater hardwood swamps in eastern North America, where enzootic transmission is maintained between the ornithophilic mosquito, Culiseta melanura, and wild passerine birds. The role of other locally abundant mosquito species in virus transmission and their associations with vertebrate hosts as sources of blood meals within these foci are largely unknown but are of importance in clarifying the dynamics of enzootic and epidemic/epizootic transmission. Blood-engorged mosqu...
Covaleda L, Fuller FJ, Payne SL.Equine infectious anemia virus (EIAV) infection is distinctive in that it causes a rapid onset of clinical disease relative to other retroviruses. In order to understand the interaction dynamics between EIAV and the host immune response, we explored the effects of EIAV and its S2 protein in the regulation of the cytokine and chemokine response in macrophages. EIAV infection markedly altered the expression pattern of a variety of pro-inflammatory cytokines and chemokines monitored in the study. Comparative studies in the cytokine response between EIAV(17) and EIAV(17DeltaS2) infection revealed ...
Zheng YH, Sentsui H, Kono Y, Ikuta K.An attenuated equine infectious anemia virus (EIAV), named V26, was previously obtained after 50 passages of the Japanese virulent strain V70 in primary macrophage culture. To clarify the differences between both viruses, their full-length sequences were determined. There were higher mutations in S2 (6.15% amino acid difference) and LTR (10.7% nucleotide difference). The presumed initiation codon of the S2 gene was absent from the sequence of V26. There was a large insertion within the long-terminal repeat (LTR) U3 hypervariable region of V26. In addition, there were minor mutations in gag (1....
Burrows R, Denyer M, Goodridge D, Hamilton F.Experimental ponies developed signs of disease four days after the intranasal instillation of A/England 1/79 equine influenza virus and virus was recovered from the nasopharynx from the second to the ninth day. No significant antigenic difference was found between the virus and the prototype A/Miami 1/63 virus, using post infection ferret and chicken sera and post vaccination pony sera. No antigenic differences were found between four viruses isolated between January and July 1979, although some differences were found in their ability to detect haemagglutination inhibiting antibody in convales...
Shakya AK, O'Callaghan DJ, Kim SK.Equine herpesvirus 1 (EHV-1) is a major pathogen affecting equines worldwide. The virus causes respiratory disease, abortion, and, in some cases, neurological disease. EHV-1 Kentucky A (KyA) is attenuated in the mouse and equine, whereas wild-type pathogenic strain RacL11 induces severe inflammatory infiltration of the lung, causing infected mice to succumb. The complete DNA sequencing of the KyA genome revealed that genes UL17 (ORF17), US6 (ORF73; gI), US7 (ORF74; gE), and US8 (ORF75; 10 K) are deleted as compared to the RacL11 and Ab4 genomes. In-frame deletions in the US1 (ORF68), US4 (OR...
Pusterla N, Gebhart C.Equine proliferative enteropathy (EPE) is a disease of foals caused by the obligate intracellular organism Lawsonia intracellularis. This organism is unique in that it causes proliferation of infected enterocytes, resulting in thickening of the intestinal epithelium, most often the small intestine. This disease affects mainly weanling foals and causes fever, lethargy, peripheral edema, diarrhea, colic and weight loss. The diagnosis of EPE may be challenging and relies on the presence of hypoproteinemia, thickening of segments of the small intestinal wall observed on abdominal ultrasonography, ...
Egberink H, Horzinek MC.Feline immunodeficiency virus (FIV) has morphological, physical and biochemical characteristics similar to human immunodeficiency virus (HIV), the cause of AIDS in man. However, it is antigenically and genetically distinct from HIV; an antigenic relatedness with equine infectious anaemia virus has been demonstrated. FIV has been molecularly cloned and sequenced. Diagnostic tests are commercially available and attempts at preparing inactivated, subunit and molecularly engineered vaccines are being made in different laboratories. During FIV infection a transient primary illness can be recognized...
O'Brien TJ, Hollinshead F, Goodrich LR.Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play...
Anderson JR, Johnson E, Jenkins R, Jacobsen S, Green D, Walters M, Bundgaard L, Hausmans BAC, van den Akker G, Welting TJM, Chabronova A, Kharaz YA....Extracellular vesicles (EVs) contribute to osteoarthritis pathogenesis through their release into joint tissues and synovial fluid. Synovial fluid-derived EVs have the potential to be direct biomarkers in the causal pathway of disease but also enable understanding of their role in disease progression. Utilizing a temporal model of osteoarthritis, we defined the changes in matched synovial fluid and plasma-derived EV small non-coding RNA and protein cargo using sequencing and mass spectrometry. Data exploration included time series clustering, factor analysis and gene enrichment interrogation. ...
