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.
Yin NH, McCarthy I, Birch HL.Human Achilles tendon is composed of three smaller sub-tendons and exhibits non-uniform internal displacements, which decline with age and after injury, suggesting a potential role in the development of tendinopathies. Studying internal sliding behaviour is therefore important but difficult in human Achilles tendon. Here we propose the equine deep digital flexor tendon (DDFT) and its accessory ligament (AL) as a model to understand the sliding mechanism. The AL-DDFT has a comparable sub-bundle structure, is subjected to high and frequent asymmetric loads and is a natural site of injury similar...
Faber E, Tshilwane SI, Kleef MV, Pretorius A.African horse sickness (AHS) is caused by African horse sickness virus (AHSV), a double stranded RNA (dsRNA) virus of the genus Orbivirus, family Reoviridae. For the development of new generation AHS vaccines or antiviral treatments, it is crucial to understand the host immune response against the virus and the immune evasion strategies the virus employs. To achieve this, the current study used transcriptome analysis of RNA sequences to characterize and compare the innate immune responses activated during the attenuated AHSV serotype 4 (attAHSV4) (in vivo) and the virulent AHSV4 (virAHSV4) (in...
Mecocci S, Porcellato I, Armando F, Mechelli L, Brachelente C, Pepe M, Gialletti R, Passeri B, Modesto P, Ghelardi A, Cappelli K, Razzuoli E.Equine genital squamous cell carcinomas (egSCCs) are among the most common equine tumors after sarcoids, severely impairing animal health and welfare. papillomavirus type 2 (EcPV2) infection is often related to these tumors. The aim of this study was to clarify the molecular mechanisms behind egSCCs associated with EcPV2 infection, investigating receptor activator of nuclear factor-kappa B ligand (RANKL) signaling in NF-kB pathway, together with the Wnt and IL17 signaling pathways. We analyzed the innate immune response through gene expression evaluation of key cytokines and transcription fac...
Townsend KS, Johnson PJ, LaCarrubba AM, Martin LM, Ericsson AC.Bacteremia resulting from dental surgery is increasingly recognized as a health risk, especially in older and immunocompromised patients. Dentistry-associated bacteremia can lead to remote infections, as exemplified by valvular endocarditis. Emerging evidence points to a novel role played by oral cavity commensals in the pathogenesis of diabetes, respiratory disease, cardiovascular disease, and adverse pregnancy outcomes. Whether dental extraction, a commonly undertaken procedure in old horses, causes bacteremia has not been reported extensively. In a prospective clinical study using next gene...
Stokes SM, Stefanovski D, Bertin FR, Medina-Torres CE, Belknap JK, van Eps AW.Endocrinopathic laminitis develops in association with insulin dysregulation, but the role of insulin in the pathogenesis remains unclear. Hyperinsulinemia can cause hypoaminoacidemia, which is associated with integumentary lesions in other species and therefore warrants investigation as a potential mechanism in laminitis. Objective: Evaluate plasma amino acid concentrations in the euglycemic-hyperinsulinemic clamp (EHC) and prolonged glucose infusion (PGI) laminitis models. Methods: Sixteen Standardbred horses. Methods: Prospective experimental study. Plasma amino acid concentrations were mea...
Laval K, Poelaert KCK, Van Cleemput J, Zhao J, Vandekerckhove AP, Gryspeerdt AC, Garré B, van der Meulen K, Baghi HB, Dubale HN, Zarak I....Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus related to pseudorabies virus (PRV) and varicella-zoster virus (VZV). This virus is one of the major pathogens affecting horses worldwide. EHV-1 is responsible for respiratory disorders, abortion, neonatal foal death and equine herpes myeloencephalopathy (EHM). Over the last decade, EHV-1 has received growing attention due to the frequent outbreaks of abortions and/or EHM causing serious economical losses to the horse industry worldwide. To date, there are no effective antiviral drugs and current vaccines do not provide full protection a...
Pan W, Shen Z, Wang H, He H.Vesicular stomatitis virus (VSV) is an archetypal member of Mononegavirales which causes important diseases in cattle, horses and pigs. The matrix protein (M) of VSV plays critical roles in the replication, assembly/budding and pathogenesis of VSV. To further investigate the role of M during viral growth, we used a two-hybrid system to screen for host factors that interact with the M protein. Here, NADH: ubiquinone oxidoreductase complex assembly factor 4 (Ndufaf4) was identified as an M-binding partner, and this interaction was confirmed by yeast cotransformation and GST pulldown assays. ...
Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, Soboll Hussey G.Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the "old mare model" to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMC...
Wimmer-Scherr C, Taminiau B, Renaud B, van Loon G, Palmers K, Votion D, Amory H, Daube G, Cesarini C.Equine atypical myopathy (AM) is caused by hypoglycin A (HGA) and methylenecyclopropylglycine (MCPG) intoxication resulting from the ingestion of seeds or seedlings of some Acer tree species. Interestingly, not all horses pasturing in the same toxic environment develop signs of the disease. In other species, it has been shown that the intestinal microbiota has an impact on digestion, metabolism, immune stimulation and protection from disease. The objective of this study was to characterize and compare fecal microbiota of horses suffering from AM and healthy co-grazers. Furthermore, potential d...
Castanheira C, Balaskas P, Falls C, Ashraf-Kharaz Y, Clegg P, Burke K, Fang Y, Dyer P, Welting TJM, Peffers MJ.Osteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potenti...
Sangiorgio DB, Hilty M, Kaiser-Thom S, Epper PG, Ramseyer AA, Overesch G, Gerber VM.Equine pastern dermatitis (EPD) is a common dermatological problem in horses, yet its aetiology and pathogenesis are poorly understood. Objective: This study aimed to investigate the effects of lesion severity and topical antimicrobial treatment on bacterial flora of EPD-affected skin. Methods: Sixteen horses with EPD were investigated. Methods: An observational study was conducted by assigning a clinical severity score ranging from 0 (macroscopically nonlesional) to 21 (severe), and sampling the most and least severely affected limbs of 16 horses (32 limbs) for bacteriological culture and 16S...
Degroote RL, Deeg CA.Horses worldwide suffer from equine recurrent uveitis (ERU), an organ-specific, immune-mediated disease with painful, remitting-relapsing inflammatory attacks alternating with periods of quiescence, which ultimately leads to blindness. In course of disease, both eyes can eventually be affected and since blind horses pose a threat to themselves and their surroundings, these animals have to be killed. Therefore, this disease is highly relevant for veterinary medicine. Additionally, ERU shows strong clinical and pathological resemblance to autoimmune uveitis in man. The exact cause for the onset ...
Zarski LM, Weber PSD, Lee Y, Soboll Hussey G.Equine herpesvirus 1 (EHV-1) affects horses worldwide and causes respiratory disease, abortions, and equine herpesvirus myeloencephalopathy (EHM). Following infection, a cell-associated viremia is established in the peripheral blood mononuclear cells (PBMCs). This viremia is essential for transport of EHV-1 to secondary infection sites where subsequent immunopathology results in diseases such as abortion or EHM. Because of the central role of PBMCs in EHV-1 pathogenesis, our goal was to establish a gene expression analysis of host and equine herpesvirus genes during EHV-1 viremia using RNA seq...
McCoy AM, Kemper AM, Boyce MK, Brown MP, Trumble TN.Post-traumatic osteoarthritis (PTOA) is a common and significant problem in equine athletes. It is a disease of the entire joint, with the synovium thought to be a key player in disease onset and progression due to its role in inflammation. The development of effective tools for early diagnosis and treatment of PTOA remains an elusive goal. Altered gene expression represents the earliest discernable disease-related change, and can provide valuable information about disease pathogenesis and identify potential therapeutic targets. However, there is limited work examining global gene expression c...
Borunova SF, Tkachev N, Iolchiev B, Artyushina Z, Abramov P, Nikitina M, Silanteva A, Khusnetdinova N, Serezhenkov V.Diseases of the gastrointestinal tract of horses are caused by many factors and have a complex pathogenesis. Developing effective methods of differential diagnostics is of high fundamental and applied importance. The pathogenesis of diseases of the digestive tract of horses accompanied by the development of inflammation and oxidative stress, can be associated with a lack of the nitrogen monoxide which controls many signaling pathways in the body. The level of the nitric oxide (NO) is involved in the regulation of the immune and nervous systems, the tone of all the blood vessels, and the course...
Conrado FO, Iapoce N, Batista-Linhares M, Lopez S, Matthews MH, McKinney CA, Rothacker C.An 18-year-old, grey, Thoroughbred Cross gelding was referred to the Cummings School of Veterinary Medicine at Tufts University following a 3-week history of low-grade fever of unknown origin, distal limb swelling, and weight loss. Clinical examination identified a few black, round, smooth nodules along the ventral aspect of the proximal tail. Transabdominal ultrasound showed a markedly enlarged heterogenous spleen, hyperechoic liver nodules, and evidence of peritonitis with fibrin deposition. A mature neutrophilia was noted on complete blood count with variable numbers of phagocytized granule...
Cymerys J, Słońska A, Chodkowski M, Golke A, Krzyżowska M, Bańbura MW.Equid herpesvirus 1 (EHV-1) causes respiratory disease, abortion and neurological disorders in horses. Similarly, to other alphaherpesviruses, EHV-1 is neurotropic and establishes latency in the neurons of its natural host. Despite the fact that many studies have been devoted to the pathogenesis of various clinical forms of EHV-1 infection, mechanisms of the neuronal damage are still not fully understood. The aim of this study was to define the phosphorylation status of tau protein in neuronal cell culture infected with EHV-1. Phosphorylation of tau was tested at tau-ser199/ser202, tau-ser404,...
Haythorn A, Young M, Stanton J, Zhang J, Mueller POE, Halper J.Equine degenerative suspensory ligament desmitis (DSLD) is a systemic connective tissue disorder first identified in Peruvian Paso horses but afflicting other horse breeds as well. Inappropriate accumulation of proteoglycans in connective tissues, most prominently in tendons and ligaments, leads to progressive and debilitating lameness and pain. It is largely unknown what drives the overproduction of proteoglycans, but our previous studies suggest involvement of bone morphogenetic protein 2 (BMP2), a member of the transforming growth factor-β (TGFβ) family, impacting synthesis of proteoglyca...
Dittmer KE, Heathcott RW, Marshall JC, Azarpeykan S.The aim of this preliminary study was to determine the relative expression of phosphatonin pathway-related genes in normal dog, sheep and horse kidneys and to explore the relationships between the different genes. Kidneys were collected post-mortem from 10 sheep, 10 horses and 8 dogs. RNA was extracted, followed by reverse transcriptase quantitative polymerase chain reaction for fibroblast growth factor receptor 1 IIIc (), sodium-phosphate co-transporter () 1 (), (), (), parathyroid hormone 1 receptor (), klotho (), vitamin D receptor (), 1a-hydroxylase () and 24-hydroxylase (). was highly ...
Albornoz A, Alarcon P, Morales N, Uberti B, Henriquez C, Manosalva C, Burgos RA, Moran G.The present work characterized the metabolomic profile of bronchoalveolar lavage fluid (BALF) in healthy horses, experimentally-induced airway inflammation by lipopolysaccharide (LPS) nebulization, and naturally-occurring asthma (n = 3 in each group). All animals underwent clinical and upper airway endoscopic examinations, and bronchoalveolar lavage. BALF supernatant samples were subjected to metabolic analysis based on gas chromatography-mass spectrometry (GC-MS). Overall, 67 peaks were obtained from BALF GC-MS analysis, corresponding to 53 metabolites which were categorized according to ch...
Journal of proteomicsSeptember 23, 2020
Volume 230 103989 doi: 10.1016/j.jprot.2020.103989
Weigand M, Hauck SM, Deeg CA, Degroote RL.Equine recurrent uveitis (ERU) is a spontaneous, remitting-relapsing autoimmune disease driven by the adaptive immune system. Although T cells are described as the main effector cells in pathogenesis, granulocytes have also emerged as possible disease mediators. To explore the role of these innate immune cells, we investigated the whole cell proteome of granulocytes from equine recurrent uveitis cases and healthy controls. Among the 2362 proteins identified by mass spectrometry, we found 96 proteins with significantly changed abundance between groups (p < 0.05, fold change >1.2), representin...
Goto Asakawa M, Mehmood W, Ali M, Oikawa MA.Myocardial atrophy with fibrosis and fatty infiltration involving the cardiac conduction system is relatively unusual in horses. We herein report of such a case in a 13-year-old Arabian broodmare that had spontaneously died on a paddock. An autopsy revealed multifocal myocardial atrophy with concomitant fibrosis and fatty infiltration in both the ventricles and interventricular septum. The Purkinje fibres in the ventricles and interventricular septum were surrounded by thick fibrous or adipose tissues adjacent to atrophic myocardial cells. Myocardial fibrosis and fatty infiltration were likely...
Saleh AG, El-Habashi N, Abd-Ellatieff HA, Abas OM, Anwar S, Fukushi H, Yanai T.Equine herpesvirus-9 (EHV-9), equine herpesvirus-1 (EHV-1) and zebra-borne EHV-1 are members of the family Herpesviridae and cause encephalitis and rhinopneumonitis in a range of animal species. The aim of this study was to characterize and compare the rhinopneumonitis induced by experimental intranasal inoculation of groups of hamsters with EHV-9, EHV-1 strain Ab4p or zebra-borne EHV-1 viruses. Animals inoculated with EHV-9 had earlier and more severe neurological and respiratory signs than those inoculated with EHV-1 strain Ab4p or zebra-borne EHV-1. At 4-5 days post inoculation (dpi), hamst...
Morandi L, Sabattini S, Renzi A, Rigillo A, Bettini G, Dervas E, Schauer A, Morandi M, Gissi DB, Tarsitano A, Evangelisti S, Tonon C.Ultra-conserved non-coding elements (UCNEs) are genomic sequences that exhibit > 95% sequence identity between humans, mammals, birds, reptiles, and fish. Recent findings reported their functional role in cancer. The aim of this study was to evaluate the DNA methylation modifications of UNCEs in squamous cell carcinoma (SCC) from different mammal species. Fifty SCCs from 26 humans, 17 cats, 3 dogs, 1 horse, 1 bovine, 1 badger, and 1 porcupine were investigated. Fourteen feline stomatitis and normal samples from 36 healthy human donors, 7 cats, 5 dogs, 5 horses, 2 bovines and 1 badger were c...
Giessler KS, Samoilowa S, Soboll Hussey G, Kiupel M, Matiasek K, Sledge DG, Liesche F, Schlegel J, Fux R, Goehring LS.Upper respiratory tract infections with Equid Herpesvirus 1 (EHV-1) typically result in a peripheral blood mononuclear cell-associated viremia, which can lead to vasculopathy in the central nervous system. Primary EHV-1 infection also likely establishes latency in trigeminal ganglia (TG) via retrograde axonal transport and in respiratory tract-associated lymphatic tissue. However, latency establishment and reactivation are poorly understood. To characterize the pathogenesis of EHV-1 latency establishment and maintenance, two separate groups of yearling horses were experimentally infected intra...
Tanaka Y, Adilbish A, Koyama K, Bayasgalan MO, Horiuchi N, Uranbileg N, Watanabe K, Purevdorj B, Gurdorj S, Banzragch B, Badgar B, Suganuma K....Dourine is a deadly protozoan disease in equids caused by infection with Trypanosoma equiperdum. Neurological signs in the later stage of infection may be caused by peripheral polyneuritis and related axonal degeneration. This neuritis involves T lymphocytes, B lymphocytes, and macrophages, and is observed in cases without obvious neurological signs. However, the pathogenesis of neuritis remains unclear. We identified M2 macrophages and CD8 T cells as the predominant phenotypes in neuritis of dourine-affected horses with or without neurological signs. In contrast, the populations of M1 macroph...
Gerhard AP, Krücken J, Heitlinger E, Janssen IJI, Basiaga M, Kornaś S, Beier C, Nielsen MK, Davis RE, Wang J, von Samson-Himmelstjerna G.P-glycoproteins (Pgp) have been proposed as contributors to the widespread macrocyclic lactone (ML) resistance in several nematode species including a major pathogen of foals, Parascaris univalens. Using new and available RNA-seq data, ten different genomic loci encoding Pgps were identified and characterized by transcriptome-guided RT-PCRs and Sanger sequencing. Phylogenetic analysis revealed an ascarid-specific Pgp lineage, Pgp-18, as well as two paralogues of Pgp-11 and Pgp-16. Comparative gene expression analyses in P. univalens and Caenorhabditis elegans show that the intestine is the maj...
Anderson JR, Phelan MM, Foddy L, Clegg PD, Peffers MJ.Osteoarthritis is an age-related degenerative musculoskeletal disease characterized by loss of articular cartilage, synovitis, and subchondral bone sclerosis. Osteoarthritis pathogenesis is yet to be fully elucidated with no osteoarthritis-specific biomarkers in clinical use. equine cartilage explants ( = 5) were incubated in tumor necrosis factor-α (TNF-α)/interleukin-1β (IL-1β)-supplemented culture media for 8 days, with the media removed and replaced at 2, 5, and 8 days. Acetonitrile metabolite extractions of 8 day cartilage explants and media samples at all time points underwent one-d...
Journal of proteomicsAugust 5, 2020
Volume 228 103927 doi: 10.1016/j.jprot.2020.103927
Chiaradia E, Pepe M, Sassi P, Mohren R, Orvietani PL, Paolantoni M, Tognoloni A, Sforna M, Eveque M, Tombolesi N, Cillero-Pastor B.Osteochondrosis is a developmental orthopedic disease affecting growing cartilage in young horses. In this study we compared the proteomes of equine chondrocytes obtained from healthy and osteochondrotic cartilage using a label-free mass spectrometry approach. Quantitative changes of some proteins selected for their involvement in different functional pathways highlighted by the bioinformatics analysis, were validated by western blotting, while biochemical alterations of extracellular matrix were confirmed via Raman spectroscopy analysis. In total 1637 proteins were identified, of which 59 wer...
Semik-Gurgul E.Sarcoids are the most commonly diagnosed skin tumours in equines. Bovine papillomaviruses (BPVs) are the primary causative agent of sarcoids. There has been intensive research to discover the molecular mechanisms that may contribute to the aetiopathogenesis of this disease and tumour suppressors and proto-oncogenes known to play a role in human neoplastic conditions have been investigated in equine sarcoids. Current approaches include the identification of gene expression profiles, characterising sarcoid and normal skin tissues, and an assessment of epigenetic alterations such as microRNA diff...
Tijms MA, Snijder EJ.Non-structural protein 1 (nsp1), the N-terminal subunit of the replicase polyprotein of the arterivirus Equine arteritis virus (EAV), is essential for viral subgenomic mRNA synthesis, but fully dispensable for genome replication. However, at the molecular level, the role of nsp1 in EAV subgenomic mRNA synthesis is poorly understood. A yeast two-hybrid screen did not reveal interactions between EAV nsp1 and other viral non-structural proteins or the nucleocapsid protein, although both nsp1 and the nucleocapsid protein were found to form homomers. Subsequently, a yeast two-hybrid screen of a HeL...
Li F, Puffer BA, Montelaro RC.Equine infectious anemia virus (EIAV) contains the simplest genome among lentiviruses in that it encodes only three putative regulatory genes (S1, S2, S3) in addition to the canonical gag, pol, and env genes, presumably reflecting its limited tropism to cells of monocyte/macrophage lineage. Tat and Rev functions have been assigned to S1 and S3, respectively, but the specific function for the S2 gene has yet to be determined. Thus, the function of S2 in virus replication in vitro was investigated by using an infectious molecular viral clone, EIAVUK. Various EIAVUK mutants lacking S2 were constr...
Côté O, Clark ME, Viel L, Labbé G, Seah SY, Khan MA, Douda DN, Palaniyar N, Bienzle D.Secretoglobin family 1A member 1 (SCGB 1A1) is a small protein mainly secreted by mucosal epithelial cells of the lungs and uterus. SCGB 1A1, also known as club (Clara) cell secretory protein, represents a major constituent of airway surface fluid. The protein has anti-inflammatory properties, and its concentration is reduced in equine recurrent airway obstruction (RAO) and human asthma. RAO is characterized by reversible airway obstruction, bronchoconstriction and neutrophilic inflammation. Direct effects of SCGB 1A1 on neutrophil functions are unknown. We have recently identified that the SC...
Fortier G, van Erck E, Pronost S, Lekeux P, Thiry E.Equine gammaherpesviruses (γEHV) have been widely studied over the past 45 years and many isolates have been characterised. Despite this, the diagnosis of γEHV infection remains difficult to establish as its clinical manifestations lack specificity, ranging from mild respiratory signs in a small number of animals to outbreaks in large groups of young horses. This review focuses on the epidemiology, pathogenesis, clinical manifestations and diagnosis of equine herpesvirus (EHV)-2 and -5 infections, as well as on the genetic variation of these viruses. Study of these variations has resulted in...
Kitamoto N, Ramig RF, Matson DO, Estes MK.The production of viral antigen after infection of MA104, HepG2 (derived from human liver), and CaCo-2 (derived from human colon) cells with various cultivatable human and animal rotavirus strains was compared using immunofluorescence tests. All rotavirus strains examined expressed antigen in CaCo-2 cells and MA104 cells, but only some virus strains, namely, SA11-Cl3 (simian), RRV (simian), CU-1 (canine), and Ty1 (turkey), produced antigen in numbers of infected HepG2 cells comparable to infections in MA104 and CaCo-2 cells. Fl-14 (equine), OSU (porcine), NCDV (bovine), and Ch2 (chicken) strai...
Brandt S, Haralambus R, Schoster A, Kirnbauer R, Stanek C.Bovine papillomaviruses of types 1 and 2 (BPV-1 and -2) chiefly contribute to equine sarcoid pathogenesis. However, the mode of virus transmission and the presence of latent infections are largely unknown. This study established a PCR protocol allowing detection of <or=10 copies of the BPV-1/-2 genes E5 and L1. Subsequent screening of peripheral blood mononuclear cell (PBMC) DNA derived from horses with and without BPV-1/2-induced skin lesions demonstrated the exclusive presence of E5, but not L1, in PBMCs of BPV-1/2-infected equines. To validate this result, a blind PCR was performed from ...
Dauvillier J, Ter Woort F, van Erck-Westergren E.Fungi contribute to the inflammatory response of lungs in horses with recurrent airway obstruction and in some forms of asthma in humans. The role of fungi in inflammatory airway disease (IAD) has not been assessed. Objective: Evaluate the prevalence of fungi in the respiratory samples of horses diagnosed with IAD, describe clinical signs associated with the presence of fungi in respiratory samples, and assess the risk factors associated with IAD and with the presence of fungi in the airways. Methods: Seven-hundred thirty-one active horses referred to a specialized ambulatory practice for sign...
Fingerhut L, Ohnesorge B, von Borstel M, Schumski A, Strutzberg-Minder K, Mörgelin M, Deeg CA, Haagsman HP, Beineke A, von Köckritz-Blickwede M....Equine recurrent uveitis (ERU) is considered one of the most important eye diseases in horses and typically appears with relapsing inflammatory episodes without systemic effects. Various disorders have been described as an initial trigger, including infections. Independent of the initiating cause, there are numerous indications that ERU is an immune-mediated disease. We investigated whether neutrophil extracellular traps (NETs) are part of the ERU pathogenesis. Therefore, vitreous body fluids (VBF), sera, and histological sections of the eye from ERU-diseased horses were analyzed for the prese...
Pacholewska A, Kraft MF, Gerber V, Jagannathan V.MicroRNAs (miRNAs) regulate post-transcriptional gene expression and may be exported from cells via exosomes or in partnership with RNA-binding proteins. MiRNAs in body fluids can act in a hormone-like manner and play important roles in disease initiation and progression. Hence, miRNAs are promising candidates as biomarkers. To identify serum miRNA biomarkers in the equine model of asthma we investigated small RNA derived from the serum of 34 control and 37 asthmatic horses. These samples were used for next generation sequencing, novel miRNA identification and differential miRNA expression ana...
Wagner B, Miller WH, Morgan EE, Hillegas JM, Erb HN, Leibold W, Antczak DF.In horses, allergies have been characterized by clinical signs and/or intradermal (i.d.) allergen testing. Our aim was to find the first direct evidence that immunoglobulin E (IgE) mediates equine allergy. In addition, we tested the hypothesis that immediate skin reactions in horses can also be mediated by IgG. Anti-IgE affinity columns were used to purify IgE from serum of one healthy horse and three horses affected with summer eczema, an allergic dermatitis which is believed to be induced by Culicoides midges. A modified Prausnitz-Küstner experiment was performed in four clinical healthy ho...
Voss KA, Norred WP, Plattner RD, Bacon CW.Currently there is no convenient bioassay to determine the potential toxicity of corn naturally contaminated with Fusarium moniliforme. A short-term bioassay would be useful for future investigations aimed at isolating as yet unidentified toxins produced by this fungus. Two groups of five male Sprague-Dawley rats were each fed one of two F. moniliforme contaminated corn samples, designated CS-1 and CS-2, that were associated with separate field cases of equine leukoencephalomalacia (ELEM). A control group, also consisting of five male rats, was fed uncontaminated seed corn. All animals survive...
Peffers MJ, McDermott B, Clegg PD, Riggs CM.The aim of the study was to characterise the protein complement of synovial fluid (SF) in health and osteoarthritis (OA) using liquid chromatography mass spectrometry (LC-MS/MS) following peptide-based depletion of high abundance proteins. Methods: SF was used from nine normal and nine OA Thoroughbred horses. Samples were analysed with LC-MS/MS using a NanoAcquity™ LC coupled to an LTQ Orbitrap Velos. In order to enrich the lower-abundance protein fractions protein equalisation was first undertaken using ProteoMiner™. Progenesis-QI™ LC-MS software was used for label-free quantification. ...
Edington N, Smyth B, Griffiths L.One of three mares in the last trimester of pregnancy became paraplegic 7 days after experimental infection with EHV-1 and was killed 10 days after infection (d.p.i.). The other two mares aborted foetuses at 12 and 14 d.p.i. In the first mare, virus was detected by immunofluorescence (IIF) and immunoperoxidase (IP) staining in endothelial cells of the endometrium, placenta and umbilical vein, but not in any other foetal tissues. In the experimentally aborted foetuses, and in two other independent field cases of abortions, endothelial cell infection was also detected in the foetuses, both in ma...
Hauck SM, Schoeffmann S, Amann B, Stangassinger M, Gerhards H, Ueffing M, Deeg CA.Spontaneous equine recurrent uveitis (ERU) is an incurable autoimmune disease affecting the eye. Although retinal-autoantigen specific T-helper 1 cells have been demonstrated to trigger disease progression and relapses, the molecular processes leading to retinal degeneration and consequent blindness remain unknown. To elucidate such processes, we studied changes in the total retinal proteome of ERU-diseased horses compared to healthy controls. Severe changes in the retinal proteome were found for several markers for blood-retinal barrier breakdown and whose emergence depended upon disease seve...
Muscatello G.Rhodococcus equi pneumonia is a worldwide infectious disease of major concern to the equine breeding industry. The disease typically manifests in foals as pyogranulomatous bronchopneumonia, resulting in significant morbidity and mortality. Inhalation of aerosolised virulent R. equi from the environment and intracellular replication within alveolar macrophages are essential components of the pathogenesis of R. equi pneumonia in the foal. Recently documented evidence of airborne transmission between foals indicates the potential for an alternative contagious route of disease transmission. In the...
Bourgeois MA, Denslow ND, Seino KS, Barber DS, Long MT.Gene expression associated with West Nile virus (WNV) infection was profiled in the central nervous system of horses. Pyrosequencing and library annotation was performed on pooled RNA from the CNS and lymphoid tissues on horses experimentally infected with WNV (vaccinated and naïve) and non-exposed controls. These sequences were used to create a custom microarray enriched for neurological and immunological sequences to quantitate gene expression in the thalamus and cerebrum of three experimentally infected groups of horses (naïve/WNV exposed, vaccinated/WNV exposed, and normal).From the sequ...
Olstad K, Ytrehus B, Ekman S, Carlson CS, Dolvik NI.Material available for research into osteochondrosis (OC) in humans tends to represent chronic lesions. Comparative studies of early lesions in young animals are, therefore, important in clarifying the pathogenesis of OC in humans. Recent studies in pigs provide strong evidence that lesions of articular OC are associated with a focal failure in the cartilage canal vascular supply to epiphyseal growth cartilage (articular-epiphyseal cartilage complex excluding the articular cartilage). The purpose of the present study was to examine histological sections from a specific predilection site for ar...
Deschene K, Céleste C, Boerboom D, Theoret CL.Exuberant granulation tissue (EGT), a fibrotic healing disorder resembling the human keloid, occurs almost exclusively in limb wounds of horses and may be caused in part by a relative state of hypoxia within the wound. Objective: The objectives of this study were therefore to (1) assess the effects of hypoxia on equine dermal fibroblast (EDF) proliferation and apoptosis, (2) study the effects of hypoxia on the expression of key extracellular matrix (ECM) associated proteins and determine if such effects are dependent on hypoxia-inducible factor (HIF), and (3) determine if EDFs from the body or...
Hedges JF, Balasuriya UB, Timoney PJ, McCollum WH, MacLachlan NJ.The persistently infected carrier stallion is the critical natural reservoir of equine arteritis virus (EAV), as venereal infection of mares frequently occurs after breeding to such stallions. Two Thoroughbred stallions that were infected during the 1984 outbreak of equine viral arteritis in central Kentucky subsequently became long-term EAV carriers. EAV genomes amplified from the semen of these two stallions were compared by sequence analysis of the six 3' open reading frames (ORFs 2 through 7), which encode the four known structural proteins and two uncharacterized glycoproteins. The major ...
Lin Q, Rikihisa Y.Diverse p44 alleles at the p44 expression locus (p44Es) encoding surface-exposed major membrane proteins, P44s, of Anaplasma phagocytophilum were hypothesized to be garnered by recombination to enact antigenic variation. However, this hypothesis has not been proven so far, due to inability to clone this obligate intragranulocytic rickettsia. To define the p44E recombination, we developed a novel method to clone A. phagocytophilum. This isogenic cloned population containing a defined p44E was used to infect a naive horse and severe combined immunodeficiency (SCID) mice. During a 58-day infectio...
Williams KJ, Robinson NE, Lim A, Brandenberger C, Maes R, Behan A, Bolin SR.Gammaherpesviruses (γHV) are implicated in the pathogenesis of pulmonary fibrosis in humans and murine models of lung fibrosis, however there is little direct experimental evidence that such viruses induce lung fibrosis in the natural host. The equine γHV EHV 5 is associated with equine multinodular pulmonary fibrosis (EMPF), a progressive fibrosing lung disease in its natural host, the horse. Experimental reproduction of EMPF has not been attempted to date. We hypothesized that inoculation of EHV 5 isolated from cases of EMPF into the lungs of clinically normal horses would induce lung fibr...
Kampen H, Holicki CM, Ziegler U, Groschup MH, Tews BA, Werner D.In 2018, West Nile virus (WNV) broke out for the first time in Germany, with continuation of the epidemic in 2019, involving birds, horses and humans. To identify vectors and characterize the virus, mosquitoes were collected in both years in zoological gardens and on a horse meadow immediately following the diagnosis of disease cases in birds and horses. Mosquitoes were identified and screened for WNV by qRT-PCR, with virus-positive samples being sequenced for the viral envelope protein gene. While no positive mosquitoes were found in 2018, seven mosquito pools tested positive for WNV in 2019 ...
Nasir L, Reid SW.The sarcoid is a benign locally invasive dermal fibroblastic lesion, commonly affecting horses and donkeys. The aetiology of the equine sarcoid is equivocal. Bovine papillomaviral (BPV) DNA (type 1/2) is frequently demonstrable in equine sarcoid tumour biopsies. However, the exact role of the virus in the disease process and its contribution to the phenotypic differences in sarcoids is not known. It was sought to assess the transcriptional activity of BPV-1 found in sarcoid tissues. Of 20 tumours examined, 18 were positive for E2 expression and ten positive for L1 expression. Viral oncogenes E...
MacLachlan NJ, Balasuriya UB, Hedges JF, Schweidler TM, McCollum WH, Timoney PJ, Hullinger PJ, Patton JF.Equine arteritis virus (EAV) is the causative agent of equine viral arteritis, an apparently emerging disease of equids. In this study, the antibody response of horses to the structural proteins of EAV was evaluated using gradient-purified EAV virions and baculovirus-expressed recombinant EAV structural proteins (G(L), G(S), M, N) as antigens in a Western immunoblotting assay. Thirty-three sera from horses that previously had been naturally or experimentally infected with EAV were evaluated, including samples from mares, geldings, and both persistently and nonpersistently infected stallions. S...
Morris DD.Endotoxemia remains the leading cause of death in horses, being intimately involved in the pathogenesis of gastrointestinal disorders that cause colic and neonatal foal septicemia. Endotoxins, normally present within the bowel, gain access to the blood across damaged intestinal mucosa, or endotoxemia occurs when gram negative organisms proliferate in tissues. Endotoxins are removed from the circulation by the mononuclear phagocyte system, and the response of mononuclear phagocytes to these lipopolysaccharides (LPS) play an important role in determining the severity of clinical disease. Macroph...
Castanheira C, Balaskas P, Falls C, Ashraf-Kharaz Y, Clegg P, Burke K, Fang Y, Dyer P, Welting TJM, Peffers MJ.Osteoarthritis remains one of the greatest causes of morbidity and mortality in the equine population. The inability to detect pre-clinical changes in osteoarthritis has been a significant impediment to the development of effective therapies against this disease. Synovial fluid represents a potential source of disease-specific small non-coding RNAs (sncRNAs) that could aid in the understanding of the pathogenesis of osteoarthritis. We hypothesised that early stages of osteoarthritis would alter the expression of sncRNAs, facilitating the understanding of the underlying pathogenesis and potenti...
Negussie H, Gizaw D, Tessema TS, Nauwynck HJ.Although equine herpesvirus myeloencephalopathy (EHM) is a sporadic and relatively uncommon manifestation of equine herpesvirus-1 (EHV-1), it has the potential for causing devastating outbreaks in horses. Up till now, there were no reported EHM outbreaks in donkeys and mules. This study describes the isolation and molecular characterization of EHV-1 from clinically EHM-affected horses (n = 6), mules (n = 3) and donkeys (n = 82) in Ethiopia during outbreaks from May 2011 to December 2013. The incidence of EHM cases was higher from April to mid-June. EHM in donkeys was more severe and deat...
Laval K, Poelaert KCK, Van Cleemput J, Zhao J, Vandekerckhove AP, Gryspeerdt AC, Garré B, van der Meulen K, Baghi HB, Dubale HN, Zarak I....Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus related to pseudorabies virus (PRV) and varicella-zoster virus (VZV). This virus is one of the major pathogens affecting horses worldwide. EHV-1 is responsible for respiratory disorders, abortion, neonatal foal death and equine herpes myeloencephalopathy (EHM). Over the last decade, EHV-1 has received growing attention due to the frequent outbreaks of abortions and/or EHM causing serious economical losses to the horse industry worldwide. To date, there are no effective antiviral drugs and current vaccines do not provide full protection a...
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...
