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Topic:Pathogenesis
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.
Residue 752 in DNA polymerase of equine herpesvirus type 1 is non-essential for virus growth in vitro. A single amino acid variation in the equine herpesvirus type 1 (EHV-1) DNA polymerase (Pol) (D752/N752) determines its neuropathogenic potential. Here, an EHV-1 strain RacL11 mutant with a deletion of Pol residue 752 was constructed. The deletion virus was then repaired to encode D752 or N752, respectively. The Delta752 mutant virus replicated with kinetics indistinguishable from those of D752 and N752 viruses. In addition, we could demonstrate that the deletion mutant was significantly more resistant to aphidicolin, a drug targeting Pol, compared with the N752 but not the D752 variant. In equ...
West Nile Virus: is a vaccine needed? West Nile virus (WNV) is a neurotropic Flavivirus that was associated with sporadic outbreaks of meningoencephalitis in Africa and the Middle East until 1999, when a more virulent strain emerged in the US that caused thousands of infections among humans and horses, with reported fatality rates between 10 and 50%. Although the epidemiology of WNV is changing into a more endemic pattern in the US, and the incidence of neuroinvasive disease is decreasing, the long-term effects of resolved WNV infections in humans, characterized as persistent movement disorders and various functional disabilities,...
Gene expression profiling from leukocytes of horses affected by osteochondrosis. Osteochondrosis (OC) is a developmental disease that affects growing horses and that severely affects their ability to perform. The genetic basis of its pathogenesis is poorly understood. The aim of the study was to analyze the transcript profile of leukocytes from horses affected with OC. Two transcriptome libraries were constructed from leukocytes of OC-affected and non-OC-affected horses using digital gene expression analysis (DGE) and real-time PCR. Statistical analysis allowed selection of 1,008 tags upregulated in the non-OC-affected group and 1,545 tags upregulated in the OC-affected gr...
Bovine papillomavirus type 1 E2 and E7 proteins down-regulate Toll Like Receptor 4 (TLR4) expression in equine fibroblasts. BPV-1 and less commonly BPV-2 are associated with the pathogenesis of equine skin tumours termed sarcoids. We recently documented the transcriptional changes that are induced by BPV-1 in equine fibroblasts using microarray analyses. TLR4 expression was found to be significantly down-regulated by BPV-1. In the present study, we show that TLR4 expression is significantly decreased following the exogenous expression of BPV-1 E2 and E7 in primary equine fibroblasts. The results were confirmed by the demonstration of increased TLR4 expression following siRNA suppression of BPV-1 E2 and E7 viral gen...
Computed tomography of temporal bone fractures and temporal region anatomy in horses. In people, specific classifications of temporal bone fractures are associated with clinical signs and prognosis. In horses, similar classifications have not been evaluated and might be useful establishing prognosis or understanding pathogenesis of certain types of trauma. Objective: We hypothesized associations between temporal bone fracture location and orientation in horses detected during computed tomography (CT) and frequency of facial nerve (CN7) deficit, vestibulocochlear nerve (CN8) deficit, or temporohyoid osteoarthropathy (THO). Complex temporal region anatomy may confound fracture id...
Differential association of MUC5AC and CLCA1 expression in small cartilaginous airways of RAO-affected and control horses. Airway mucus accumulation is associated with indoor irritant and allergen exposure in horses with recurrent airway obstruction (RAO). Epidermal growth factor receptor (EGFR) and a chloride channel (calcium activated, family member 1; CLCA1) are key signalling molecules involved in mucin gene expression. Objective: We hypothesised that exposure to irritants and aeroallergens would lead to increased expression of the mucin gene eqMUC5AC and increased stored mucosubstance in the airways of RAO-affected horses, associated with increased neutrophils and CLCA1 and EGFR mRNA levels. Methods: We perfo...
In vitro bioassay to detect reaginic antibodies from the serum of horses affected with recurrent airway obstruction. In horses, Recurrent Airway Obstruction (RAO) is an allergic disease that involves IgE mediated Type I Hypersensitivity responses. The development of this type of allergy involves a series of events that begins with reaginic antibodies, mainly IgE and some IgG subclasses. These reaginic antibodies bind with high affinity, via the Fc portion, to FcepsilonRI receptors on the membrane of mast cells and basophils. Once bound, environmental allergens cross-link the antibodies, which results in mast cell degranulation leading to the production of histamine and other chemical mediators that act toget...
[The difference in specific humoral immune responses induced with the attenuated equine infectious anemia vaccine strain and virulent strain.]. To disclose the potential roles of humoral immune response in the EIAV vaccine-induced protective immunity. In this study, major parameters of humoral immunity be compared between horses inoculated with the EIAV vaccine strain and the pathogenic virulent strain. Methods: Experimental horses were randomly assigned into the group inoculated with the vaccine strain EIAV(DLV); (the vaccinated group) and the group inoculated with sub-morbigenous dose of virulent strain EIAV(Liao); (the inapparent infection group). Humoral immunity parameters, including binding endpoint titer and avidity index of an...
Markers of the uterine innate immune response of the mare. Reproductive efficiency in mares is low and persistent mating-induced endometritis (PMIE) is an important cause of subfertility. Mating-induced endometritis (MIE) an obligate precursor to PMIE, is a ubiquitous, transient inflammatory response to the presence of sperm, seminal components and pathogens. However, the specific inflammatory pathways that derive from MIE and that may also be precursors to PMIE are not clear. The ability to identify and measure robust, repeatable markers of inflammation integral to MIE may be key to understanding the progression to PMIE. The aim of the study was to (...
Characterization of a thymidine kinase-deficient mutant of equine herpesvirus 4 and in vitro susceptibility of the virus to antiviral agents. Equine herpesvirus 4 (EHV-4) is an important equine pathogen that causes respiratory tract disease among horses worldwide. A thymidine kinase (TK)-deletion mutant has been generated by using bacterial artificial chromosome (BAC) technology to investigate the role of TK in pathogenesis. Deletion of TK had virtually no effect on the growth characteristics of WA79DeltaTK in cell culture when compared to the parent virus. Also, virus titers and plaque formation were unaffected in the absence of the TK gene. The sensitivity of EHV-4 to inhibition by acyclovir (ACV) and ganciclovir (GCV) was studied...
EIAV S2 enhances pro-inflammatory cytokine and chemokine response in infected macrophages. 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 ...
Equine laminitis: ultrastructural lesions detected in ponies following hyperinsulinaemia. Anatomical changes in the hoof lamellar tissue induced by prolonged hyperinsulinaemia have not been described previously. Analysis of the induced lesions may promote understanding of hyperinsulinaemic laminitis pathogenesis and produce clinical benefit. Objective: To use light and transmission electron microscopy (TEM) to document hoof lamellar lesions in ponies clinically lame after prolonged hyperinsulinaemia. Methods: Nine clinically normal, mature ponies were allocated randomly to either a treatment group (n = 5) or control group (n = 4). The treatment group received insulin via a modified...
Equine immune-mediated keratopathies. Equine immune mediated keratopathies are common in both Europe and the USA. This review article will compare the clinical differences in horses with this disease and also review the current theories on pathogenesis and treatment of equine IMMK.
Pathology of gastritis and gastric ulceration in the horse. Part 1: range of lesions present in 21 mature individuals. Gastric ulceration is now widely recognised as an important disease in high performance horses. Little is known about gastric histopathology in healthy or diseased animals; a comprehensive assessment would enhance interpretation of gross findings through assessment of their accuracy and allow for identification of lesion variety and pathogenesis in different anatomical regions of the stomach. Objective: To investigate the true extent and variety of gastric lesions in a mixed population of mature horses at post mortem. Methods: Stomachs were removed from a mixed population of 21 horses at post ...
Pathology of gastritis and gastric ulceration in the horse. Part 2: a scoring system. High numbers of racehorses in training are reported to have gastric ulceration. Gross lesion scoring systems exist, but there is no fixed protocol with which to record gastric microscopic findings. In man, the histological classification of stomach lesions helps in the identification of recognised and emerging aetiologies of gastric disease and aids accurate comparison of findings between studies. In horses, the development of such a system would therefore be of benefit. Objective: To develop a pathological scoring system that can be applied to examine samples of the equine stomach at biopsy a...
Development of a novel equine whole transcript oligonucleotide GeneChip microarray and its use in gene expression profiling of normal articular-epiphyseal cartilage. No large scale equine microarray is available commercially to allow genomic and transcriptional profiling of the majority of genes that would define the genetic basis of equine disease. Objective: To generate a whole transcript target labelled GeneChip to interrogate the equine transcriptome and validate chip performance using RNA samples derived from organs, articular cells and normal cartilage. Methods: Equine mRNA and selected equine gene sequences derived from perfect cross-hybridisation of equine RNA on human microarray GeneChips, were used to design a custom equine gene microarray. Seque...
Equine bronchial epithelial cells differentiate into ciliated and mucus producing cells in vitro. We describe a method for creating differentiated equine bronchial epithelial cell cultures that can be used for in vitro studies including airway disease mechanisms and pathogen-host interactions. Our method is based on the culturing of human tracheobronchial epithelial cells at an air-liquid interface (ALI) in specific serum-free, hormone-supplemented medium. Bronchial epithelial cells are isolated and grown on T-Clear® insert membranes. Within 2 to 3 wk, cells differentiate into ciliated and mucus producing cells as demonstrated by confocal and electron microscopy. Furthermore, the demonstr...
Differences in replication kinetics and cell tropism between neurovirulent and non-neurovirulent EHV1 strains during the acute phase of infection in horses. Equine herpesvirus 1 (EHV1) replicates in the respiratory tract of horses, after which infected leukocytes transport virus throughout the body, resulting in abortion or nervous system disorders. Two EHV1 strains circulate in the field: neurovirulent and non-neurovirulent. To investigate differences in replication in the upper respiratory tract (URT), an experimental inoculation study in ponies was performed with both strains. Two groups of six ponies, were inoculated intranasally with 10(6.5) TCID(50) of either strain. Clinical signs, nasal shedding and viremia were evaluated. At early time po...
Regional distribution of collagen and haemosiderin in the lungs of horses with exercise-induced pulmonary haemorrhage. Regional veno-occlusive remodelling of pulmonary veins in EIPH-affected horses, suggests that pulmonary veins may be central to pathogenesis. The current study quantified site-specific changes in vein walls, collagen and haemosiderin accumulation, and pleural vascular profiles in the lungs of horses suffering EIPH. Objective: In the caudodorsal lung regions of EIPH-affected horses, there is veno-occlusive remodelling with haemosiderosis, angiogenesis and fibrosis of the interstitium, interlobular septa and pleura. Methods: Morphometric methods were used to analyse the distribution and accumula...
Equine cyathostomins: a review of biology, clinical significance and therapy. The small strongyles of horses, also known as cyathostomins, are considered the most prevalent and pathogenic parasites of horses today. The clinical syndrome of larval cyathostominosis which occurs as a result of mass emergence of inhibited stages has a high fatality rate despite the best standard of care given to affected horses. Management of the challenge level of cyathostomins to prevent the syndrome is preferable. Many different management programmes have been tried over the past two decades, with mixed success. Programmes have relied heavily on repeated use of anthelmintic treatments th...
IgE in horses: occurrence in health and disease. Since the initial characterization of IgE by Ishizaka et al. (1966), IgE was described in several mammalian species. In horses, a single gene encoding the IgE heavy chain constant region (IGHE gene) exists per haploid genome and several allelic variants of the equine IGHE gene were found. IgE occurs in its soluble form in equine serum and physiological concentrations of total IgE are around 1000-fold higher in normal horse than in normal human serum. Maternal IgE is enriched in the colostrum and transferred to the neonatal foal after birth. Foals do not produce detectable concentrations of end...
[Construction and in vitro evaluation of an infectious clone of the equine infectious anemia virus vaccine strain EIAV(FDDV) with four reverse-mutated vaccine-specific sites in the S2 gene]. To elucidate the function of the S2 gene in equine infectious anemia virus (EIAV) and its role in the attenuation of the Chinese attenuated EIAV vaccine strains, the S2 in the EIAV vaccine strain EIAV (FDDV) was reverse-mutated and the in vitro replication character of the resultant virus was evaluated. Based on the sequence variation of the S2 gene between the EIAV virulent strains and vaccine strains, all the four vaccine-specific sites in the S2 of an EIAV(FDDV) infectious clone, pFDDV3-8, were reverse-mutated to the sequences of the virulent strain EIAV(DV115). The reverse-mutated molecula...
Equine gammaherpesviruses: pathogenesis, epidemiology and diagnosis. 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...
Plasma and pulmonary fluid endothelin in horses with seasonal recurrent airway obstruction. Summer pasture-associated recurrent airway obstruction (SPA-RAO), a seasonal airway obstructive disease of horses, is characterized by clinical exacerbation after exposure to pasture during warm months of the year. Endothelin (ET)-1, potent bronchoconstrictor, mitogen, secretagogue, and proinflammatory mediator, has been implicated in the pathogenesis of asthma and equine heaves. Objective: Immunoreactive ET-1 concentrations increase during clinical exacerbation and return to basal values during periods of disease remission. Methods: Twelve horses, 6 affected with SPA-RAO and 6 nonaffected. Me...
Kininogen in autoimmune uveitis: decrease in peripheral blood stream versus increase in target tissue. Equine recurrent uveitis (ERU) is an incurable disease affecting the inner eye that leads to blindness, through activated T cells that pass the blood-retinal barrier and destroy the retina. Serum markers are a desirable choice for monitoring development of disease, as serum is easy accessible and the markers could serve to predict the beginning of disease or an imminent relapse. Methods: In this study, serum proteomes (depleted of high-abundance serum proteins) of horses with ERU and healthy controls were compared with the 2-D DIGE (two-dimensional gel electrophoresis) technique to identify di...
Bovine papillomavirus type 1 oncoprotein E5 inhibits equine MHC class I and interacts with equine MHC I heavy chain. Bovine papillomavirus type 1 is one of the aetiological agents of equine sarcoids. The viral major oncoprotein E5 is expressed in virtually all sarcoids, sarcoid cell lines and in vitro-transformed equine fibroblasts. To ascertain whether E5 behaves in equine cells as it does in bovine cells, we introduced the E5 open reading frame into fetal equine fibroblasts (EqPalF). As observed in primary bovine fibroblasts (BoPalF), E5 by itself could not immortalize EqPalF and an immortalizing gene, such as human telomerase (hTERT/hT), was required for the cells to survive selection. The EqPalF-hT-1E5 c...
The increased prevalence of neuropathogenic strains of EHV-1 in equine abortions. A panel of 426 archived EHV-1 isolates collected (1951-2006) from equine abortions was analyzed using a real-time Taq-Man((R)) allelic discrimination PCR assay. Based on previous findings, isolates possessing adenine at nucleotide position 2254 (A(2254)) in ORF30 were classified as having a non-neuropathogenic genotype and those with guanine at 2254 (G(2254)) were designated as the neuropathogenic genotype. The resultant data demonstrated that viruses with the neuropathogenic genotype existed in the 1950s and isolates with this genotype increased from 3.3% in the 1960s to 14.4% in the 1990s. T...
Analysis of complete genome sequence of Neorickettsia risticii: causative agent of Potomac horse fever. Neorickettsia risticii is an obligate intracellular bacterium of the trematodes and mammals. Horses develop Potomac horse fever (PHF) when they ingest aquatic insects containing encysted N. risticii-infected trematodes. The complete genome sequence of N. risticii Illinois consists of a single circular chromosome of 879 977 bp and encodes 38 RNA species and 898 proteins. Although N. risticii has limited ability to synthesize amino acids and lacks many metabolic pathways, it is capable of making major vitamins, cofactors and nucleotides. Comparison with its closely related human pathogen N. senn...
Equine herpesvirus-1 consensus statement. Equine herpesvirus-1 is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). In recent years, there has been an apparent increase in the incidence of EHM in North America, with serious consequences for horses and the horse industry. This consensus statement draws together current knowledge in the areas of pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment.
Update on treatments for endotoxemia. Endotoxemia is a major cause of morbidity and mortality in horses affected by colic. This article briefly reviews the pathogenesis of endotoxemia in horses with colic, reviews current established treatments, and describes new advances in the treatment of endotoxemia.
