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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.
Changes in matrix metalloproteinase network in a spontaneous autoimmune uveitis model. Autoimmune uveitis is a sight-threatening disease in which autoreactive T cells cross the blood-retinal barrier. Molecular mechanisms contributing to the loss of eye immune privilege in this autoimmune disease are not well understood. In this study, the authors investigated the changes in the matrix metalloproteinase network in spontaneous uveitis. Methods: Matrix metalloproteinase (MMP) MMP2, MMP9, and MMP14 expression and tissue inhibitor of metalloproteinase (TIMP)-2 and lipocalin 2 (LCN2) expression were analyzed using Western blot quantification. Enzyme activities were examined with zymog...
p38 mitogen-activated protein kinase is crucial for bovine papillomavirus type-1 transformation of equine fibroblasts. Equine sarcoids represent the most common skin tumours in equids worldwide, characterized by extensive invasion and infiltration of lymphatics, rare regression and high recurrence after surgical intervention. Bovine papillomavirus type-1 (BPV-1) and less commonly BPV-2 are the causative agents of the diseases. It has been demonstrated that BPV-1 viral gene expression is necessary for maintaining the transformation phenotype. However, the underlying mechanism for BPV-1 transformation remains largely unknown, and the cellular factors involved in transformation are not fully understood. Previousl...
Recurrent Actinobacillus peritonitis in an otherwise healthy thoroughbred horse. A Thoroughbred gelding in North America was evaluated for Actinobacillus peritonitis on three different occasions over a 4-year period. At each presentation, peritoneal fluid had an elevated nucleated cell count (220,000-550,000 cells/µL) characterised by non-degenerate neutrophils, no visible bacteria, an elevated total protein (4.6-5.5 g/dL) and bacterial culture yielding Actinobacillus spp. Actinobacillus peritonitis appears to be a regional disease occurring in Australia and less commonly in New Zealand and North America. Recurrence, other than incomplete resolution, has not been previous...
Molecular evolution of the six internal genes of H5N1 equine influenza A virus. Phylogenetic and evolutionary patterns of the six internal genes of an equine H5N1 influenza A virus isolated in Egypt on 2009 were analyzed using direct sequencing. All of the internal genes of the equine H5N1 strain showed a genetic pattern potentially related to Eurasian lineages. Variable dendrogram topologies revealed an absence of reassortment in the equine strain while confirming its close relatedness to other Egyptian H5N1 strains from human and avian species. The equine strain is characterized by a variety of amino acid substitutions in six internal proteins compared to the available ...
Role of oxidative tissue injury in the pathophysiology of experimentally induced equine laminitis: a comparison of 2 models. Oxidative stress reportedly plays a role in sepsis-induced organ dysfunction and failure in many species. In septic horses, laminae are targeted; evidence of laminar oxidative stress has been reported experimentally in the black walnut extract (BWE) model. Carbohydrate (CHO)-induced laminitis may be more similar to clinical sepsis-related laminitis than the BWE model in that animals with CHO-induced disease commonly develop laminar failure. The role of oxidative stress in the CHO model remains unknown. Objective: Markers of oxidative stress will be increased in laminae from horses with BWE- an...
Decreased expression of p63, a regulator of epidermal stem cells, in the chronic laminitic equine hoof. Abnormal epidermal stem cell regulation may contribute to the pathogenesis of equine chronic laminitis. Objective: To analyse the involvement of p63, a regulator of epidermal stem cell proliferative potential, in chronic laminitis. Methods: Epidermal tissues from skin, coronet and lamellae of the dorsal foot were harvested from 5 horses with chronic laminitis and 5 control horses. Tissues were analysed using histopathology, immunofluorescence microscopy and quantitative immunoblotting. Results: Hoof lamellae of laminitic horses had a lower frequency of p63 positive cells than control lamellae,...
Expression of Toll-like receptors 2, 3, 4, 6, 9, and MD-2 in the normal equine cornea, limbus, and conjunctiva. Human corneal cells have detectable levels of TLRs 1-10. TLRs 2 and 4 are the major corneal receptors, recognizing the PAMPs associated with fungal invasion in humans. The conjunctiva and limbus contain TLRs 2, 4, and 9. Our purpose was to determine the expression of TLRs 2, 3, 4, 6, 9, and MD-2 in the normal equine cornea, conjunctiva, and limbus. Methods: Corneal, limbal, and conjunctival tissues were collected from seven euthanized horses having no evidence of ocular disease. RNA extraction with DNase-1 digestion was performed followed by RT-PCR to determine expression of TLRs 2, 3, 4, 6, 9...
The UL4 protein of equine herpesvirus 1 is not essential for replication or pathogenesis and inhibits gene expression controlled by viral and heterologous promoters. Defective interfering particles (DIP) of equine herpesvirus 1 (EHV-1) inhibit standard virus replication and mediate persistent infection. The DIP genome is comprised of only three genes: UL3, UL4, and a hybrid gene composed of portions of the IR4 (EICP22) and UL5 (EICP27) genes. The hybrid gene is important for DIP interference, but the function(s) of the UL3 and UL4 genes are unknown. Here, we show that UL4 is an early gene activated solely by the immediate early protein. The UL4 protein (UL4P) was detected at 4hours post-infection, was localized throughout the nucleus and cytoplasm, and was...
Early lesions of articular osteochondrosis in the distal femur of foals. Failure of the cartilage canal blood supply to epiphyseal growth cartilage has been implicated in the pathogenesis of articular osteochondrosis in horses and other animal species. In a previous study of the developmental pattern of the blood supply in the tarsus of foals, early lesions of osteochondrosis were consistently found in regions where the cartilage canal vessels traversed the chondro-osseous junction. The developmental pattern of blood vessels has also been described in the distal femoral epiphysis; however, the group of foals examined in that study did not have lesions of osteochond...
Evaluation of immune responses following infection of ponies with an EHV-1 ORF1/2 deletion mutant. Equine herpesvirus-1 (EHV-1) infection remains a significant problem despite the widespread use of vaccines. The inability to generate a protective immune response to EHV-1 vaccination or infection is thought to be due to immunomodulatory properties of the virus, and the ORF1 and ORF2 gene products have been hypothesized as potential candidates with immunoregulatory properties. A pony infection study was performed to define immune responses to EHV-1, and to determine if an EHV-1 ORF1/2 deletion mutant (ΔORF1/2) would have different disease and immunoregulatory effects compared to wild type EH...
Phosphoinositides direct equine infectious anemia virus gag trafficking and release. Phosphatidylinositol 4,5-biphosphate [PI(4,5)P(2) ], the predominant phosphoinositide (PI) on the plasma membrane, binds the matrix (MA) protein of human immunodeficiency virus type 1 (HIV-1) and equine infectious anemia virus (EIAV) with similar affinities in vitro. Interaction with PI(4,5)P(2) is critical for HIV-1 assembly on the plasma membrane. EIAV has been shown to localize in internal compartments; hence, the significance of its interaction with PI(4,5)P(2) is unclear. We therefore investigated the binding in vitro of other PIs to EIAV MA and whether intracellular association with comp...
Isolation of an equine coronavirus from adult horses with pyrogenic and enteric disease and its antigenic and genomic characterization in comparison with the NC99 strain. A new equine coronavirus was isolated from the feces of adult horses with pyrogenic and enteric disease. The disease outbreak was mainly observed among 2- to 4-year-old horses living in stables of a draft-horse racetrack in Japan. On comparing the isolated virus (isolate Tokachi09) with the equine coronavirus NC99 strain, no significant differences were observed in several biological properties such as hemagglutinating activity, antigenicity (in indirect immunofluorescence and neutralization tests), and one-step growth (in cell culture). The sequences of the nucleocapsid and spike genes of iso...
Immunological characterization of the equine airway epithelium and of a primary equine airway epithelial cell culture model. Our understanding of innate immunity within the equine respiratory tract is limited despite growing evidence for its key role in both the immediate defense and the shaping of downstream adaptive immune responses to respiratory disease. As the first interface to undergo pathogen invasion, the respiratory epithelium is a key player in these early events and our goal was to examine the innate immune characteristics of equine respiratory epithelia and compare them to an in vitro equine respiratory epithelial cell model cultured at the air-fluid interface (AFI). Respiratory epithelial tissues, isol...
Identification of mixed equine rhinitis B virus infections leading to further insight on the relationship between genotype, serotype and acid stability phenotype. Equine rhinitis B virus (ERBV) is the single species in the genus Erbovirus, family Picornaviridae. Equine rhinitis B viruses exist in three serotypes and are associated with respiratory disease in horses. Members of the species vary in stability at acid pH. To date there has been discordance in genotype, serotype and acid stability phenotype groupings. To identify capsid regions associated with acid stability, two viruses were serially treated at pH 3.3 to isolate acid-stable mutants. An acid-stable mutant of the prototype acid-labile serotype 1 virus contained a single amino acid change in t...
Properties of an equine herpesvirus 1 mutant devoid of the internal inverted repeat sequence of the genomic short region. The 150 kbp genome of equine herpesvirus-1 (EHV-1) is composed of a unique long (UL) region and a unique short (Us) segment, which is flanked by identical internal and terminal repeat (IR and TR) sequences of 12.7 kbp. We constructed an EHV-1 lacking the entire IR (vL11ΔIR) and showed that the IR is dispensable for EHV-1 replication but that the vL11ΔIR exhibits a smaller plaque size and delayed growth kinetics. Western blot analyses of cells infected with vL11ΔIR showed that the synthesis of viral proteins encoded by the immediate-early, early, and late genes was reduced at immediate-early...
Evaluation of cytokine mRNA expression in bronchoalveolar lavage cells from horses with inflammatory airway disease. Inflammatory airway disease (IAD) is a common disorder of performance horses and is associated with poor performance and accumulation of mucus and inflammatory cells in lower airway secretions. Horses with IAD frequently have increased relative counts of neutrophils in bronchoalveolar lavage fluid (BALF); less commonly relative counts of eosinophils and/or mast cells may be increased. The aetiopathogenesis of IAD is unknown and may involve innate and/or acquired immune responses to various factors including respirable dust constituents, micro-organisms, noxious gases and unconditioned air. The...
Histopathology of insulin-induced laminitis in ponies. Ponies with laminitis associated with insulin resistance and hyperinsulinaemia lack systemic and/or intestinal inflammatory signs, suggesting a different pathogenesis potentially reflected in differing histopathology. Objective: To describe the histological appearance and quantify morphological changes in primary and secondary epidermal lamellae (PEL and SEL) of laminitis lesions from ponies with insulin-induced laminitis. Methods: Equine hoof lamellar tissue was obtained from 4 control ponies and 5 ponies with laminitis induced following infusion of insulin (1036 ± 55 µU/ml) while maintai...
Equine herpesvirus-1 infected peripheral blood mononuclear cell subpopulations during viremia. Infection with equine herpesvirus-1 (EHV-1) causes respiratory disease, late term abortions and equine herpesvirus myeloencephalitis (EHM) and remains an important problem in horses worldwide. Despite increasing outbreaks of EHM in recent years, our understanding of EHM pathogenesis is still limited except for the knowledge that a cell-associated viremia in peripheral blood mononuclear cells (PBMCs) is a critical link between primary respiratory EHV-1 infection and secondary complications such as late-term abortion or EHM. To address this question our objective was to identify which PBMC subpo...
Pathological changes caused by Anoplocephala perfoliata in the mucosa/submucosa and in the enteric nervous system of equine ileocecal junction. In this study, pathological changes caused by Anoplocephala perfoliata in the ileocecal junction were investigated in 31 regularly slaughtered mixed-breed horses of both sexes. Our results showed a significant relationship between parasite burden and grading of histopathological lesions in the mucosa and submucosa. Hypertrophy of the circular muscle layer was found in infected horses. Moreover, enteric nervous system evaluation showed a significant injury of intestinal nervous elements in the horses with moderate to high parasitism expressed as an increase of degenerative-regressive changes in...
Geotrichum candidum as etiological agent of horse dermatomycosis. Fungi of the genus Geotrichum are commonly found in the environment and, in some circumstances, they may cause diseases in humans and animals. Although these fungi have been isolated from skin lesions of some animal species, their pathogenic role in horses remains uncertain. With the aim to investigate the role of Geotrichum candidum as etiological agent of dermatomycoses, a retrospective study of 64 horses presenting skin lesions and suspected to have fungal infections was carried out. For each animal, anamnestic data were recorded and fungal culture were performed using hair. Out of 64 cases...
Bovine papillomavirus E7 oncoprotein binds to p600 in naturally occurring equine sarcoids. Studies regarding the functions of the bovine papillomavirus (BPV) E7 oncoprotein in vivo are lacking and no E7-mediated mechanism underlying mesenchymal carcinogenesis is known. Here, we show that the interaction between the 600 kDa retinoblastoma protein-associated factor (p600) and BPV E7, described in vitro in cultured cells, takes place in vivo in naturally occurring equine sarcoids. In these cancers we detect the expression of E7 and p600, and demonstrate that E7 and p600 co-localize and physically interact. Furthermore, intracellular signals involved in p600 functional activity are foun...
Selective cloning, characterization, and production of the Culicoides nubeculosus salivary gland allergen repertoire associated with equine insect bite hypersensitivity. Salivary gland proteins of Culicoides spp. have been suggested to be among the main allergens inducing IgE-mediated insect bite hypersensitivity (IBH), an allergic dermatitis of the horse. The aim of our study was to identify, produce and characterize IgE-binding salivary gland proteins of Culicoides nubeculosus relevant for IBH by phage surface display technology. A cDNA library constructed with mRNA derived from C. nubeculosus salivary glands was displayed on the surface of filamentous phage M13 and enriched for clones binding serum IgE of IBH-affected horses. Ten cDNA inserts encoding putat...
Therapy of equine infectious keratitis: a review. The following article briefly discusses the pathogenesis of infectious keratitis in the horse, followed by discussion of management and pharmacological aspects to be considered when devising a therapeutic protocol for affected patients.
Analysis of the subchondral microarchitecture of the distopalmar aspect of the third metacarpal bone in racing Thoroughbreds. To determine the anisotropic characteristics of the microarchitecture of the subchondral bone (SCB) plate and trabecular bone (TBB) of the distopalmar aspect of the metacarpal condyles in horses with different stages of SCB disease. Methods: 12 third metacarpal bone pairs from racing Thoroughbreds euthanized for diverse reasons. Methods: Both metacarpi were collected from horses with SCB changes that were mild (sclerosis and focal radiolucencies; n=6) or severe (multifocal radiolucencies and articular surface defects; 6). Sample blocks of SCB plate and TBB were collected from the distopalmar a...
Expression of genes associated with inflammation induced by ex vivo exposure to lipopolysaccharide in peripheral blood leukocytes from horses with gastrointestinal disease. To investigate the effect of ex vivo exposure to lipopolysaccharide (LPS) on the expression of inflammatory genes in leukocytes from horses with gastrointestinal (Gl) disease and determine whether the pattern or magnitude of the response to LPS correlated with the type of disease and outcome. Methods: 49 horses with Gl disease and 10 healthy horses Methods: Leukocytes were isolated from blood samples and submitted to 3 protocols: immediate freezing, freezing after 4-hour incubation in medium, and freezing after 4-hour incubation in medium containing LPS. Expression of 14 genes associated with ...
The OARSI histopathology initiative – recommendations for histological assessments of osteoarthritis in the horse. Equine models of osteoarthritis (OA) have been used to investigate pathogenic pathways of OA and evaluate therapeutic candidates for naturally occurring equine OA which is a significant clinical disease in the horse. This review focuses on the macroscopic and microscopic criteria for assessing naturally occurring OA in the equine metacarpophalangeal joint as well as the osteochondral fragment-exercise model of OA in the equine middle carpal joint. Methods: A review was conducted of all published OA studies using horses and the most common macroscopic and microscopic scoring systems were summar...
Adaptation of Staphylococcus aureus to ruminant and equine hosts involves SaPI-carried variants of von Willebrand factor-binding protein. Staphylococci adapt specifically to various animal hosts by genetically determined mechanisms that are not well understood. One such adaptation involves the ability to coagulate host plasma, by which strains isolated from ruminants or horses can be differentiated from closely related human strains. Here, we report first that this differential coagulation activity is due to animal-specific alleles of the von Willebrand factor-binding protein (vWbp) gene, vwb, and second that these vwb alleles are carried by highly mobile pathogenicity islands, SaPIs. Although all Staphylococcus aureus possess c...
Meniscal translocation and deformation throughout the range of motion of the equine stifle joint: an in vitro cadaveric study. By study of the translocation and deformation of equine menisci throughout the range of motion, it may be possible to identify potential mechanical factors in the pathogenesis of injury to the cranial horn of the medial meniscus. Objective: To quantitatively document meniscal translocation and deformation using radiographic and MR imaging, and to evaluate for potential variation between the medial and lateral menisci. Methods: Radiographic markers were embedded in the periphery of the menisci in 6 cadaver stifles. Proximal-distal radiographs were taken at 15° intervals ranging from full flexi...
West Nile virus lineage 2 as a cause of zoonotic neurological disease in humans and horses in southern Africa. West Nile virus (WNV) is widely distributed in South Africa, but since a few cases of neurological disease have been reported from this region, endemic lineage 2 strains were postulated to be of low virulence. Several cases of nonfatal encephalitis in humans as well as fatal cases in a foal, dog, and ostrich chicks have, however, been associated with lineage 2 WNV in South Africa. The pathogenesis of lineage 2 WNV strains was investigated using mouse neuroinvasive experiments, gene expression experiments, and genome sequence comparisons which indicated that lineage 2 strains that are highly pa...
Horses naturally infected by Trypanosoma vivax in southern Brazil. In this study, we reported the first outbreak of the infection by Trypanosoma vivax in horses in southern Brazil, a non-endemic region where bovines have only recently been found infected by this trypanosome species. We evaluated 12 horses from a farm in southern Brazil, where four horses displayed pale mucous membranes, fever, weight loss, and swelling of abdomen, prepuce, or vulva. The diagnosis of T. vivax was confirmed in four horses by morphological parameters of trypomastigotes in blood smears and species-specific PCR. All T. vivax-infected animals showed anemia, and most showed increase...
