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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.
Functional characterization of EUL47 in productive replication, morphogenesis and infectivity of equine herpesvirus 1. EUL47 is a major component of the tegument of equine herpesvirus 1 (EHV-1). To determine its function, we used Red/ET cloning to delete its gene (gene 13) from EHV-1 strain Ab4p inserted into a bacterial artificial chromosome (BAC), yielding Ab4pattBΔ13. We also examined the reverted virus (Ab4pattB13R). Ab4pattBΔ13 replicated in rabbit kidney (RK)-13 cells, indicating that ORF13 is dispensable for virus replication in cell culture. Its intracellular and extracellular titers were about 10- and 100-fold lower than those of the revertant and parent strains, respectively. In addition, the plaqu...
MyD88-dependent recruitment of monocytes and dendritic cells required for protection from pulmonary Burkholderia mallei infection. The Gram-negative bacterium Burkholderia mallei causes rapidly fatal illness in equines and humans when contracted by inhalation and also has the potential to be used as a bioweapon. However, little is known regarding the early innate immune responses and signaling mechanisms required to generate protection from pneumonic B. mallei infection. We showed previously that monocyte chemoattractant protein 1 (MCP-1) was a critical chemokine required for protection from pneumonic B. mallei infection. We have now extended those studies to identify key Toll-like receptor (TLR) signaling pathways, effec...
Persistent digital hyperthermia over a 48 h period does not induce laminitis in horses. Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl(2) was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48 h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an inter...
Advanced imaging of the nervous system in the horse. Neuroimaging underwent a dramatic revolution during the past few decades due to the development of new technologies that produce exquisite images of patient morphology and function, new technologies that store and distribute information more efficiently, and research that has improved understanding of pathogenesis and effective clinical use of new imaging methods. Advanced equine neuroimaging is a specialized field with unique challenges associated with patient size, availability of equipment, using equipment designed for humans, small sample size for various diseases, and issues associated wi...
Rhodococcus equi pneumonia in the foal–part 1: pathogenesis and epidemiology. 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...
Rhodococcus equi: clinical manifestations, virulence, and immunity. Pneumonia is a major cause of disease and death in foals. Rhodococcus equi, a gram-positive facultative intracellular pathogen, is a common cause of pneumonia in foals. This article reviews the clinical manifestations of infection caused by R. equi in foals and summarizes current knowledge regarding mechanisms of virulence of, and immunity to, R. equi. A complementary consensus statement providing recommendations for the diagnosis, treatment, control, and prevention of infections caused by R. equi in foals can be found in the same issue of the Journal.
Characterization of cytokines associated with Th17 cells in the eyes of horses with recurrent uveitis. Equine recurrent uveitis (ERU) is a spontaneous disease that is the most common cause of blindness in horses, affecting up to 15% of the horse population. Th17 cells are a major cell population driving the pathogenesis in several mouse models of autoimmune inflammation, including experimental autoimmune uveitis. The purpose of this study is to investigate the role a Th17 cell-mediated response plays in the pathogenesis of ERU. Methods: Banked, Davidson's-fixed equine globes histopathologically diagnosed with ERU (n = 7) were compared immunohistochemically with healthy control globes (n = 7). I...
Gene expression analysis in the thalamus and cerebrum of horses experimentally infected with West Nile virus. 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...
Brittle tail syndrome is an emerging infection in horses caused by a keratinolytic fungus Equicapillimyces hongkongensis gen. nov., sp. nov. The newly described brittle tail syndrome causes weakening and breakage of the tail hair of horses. Extensive mycological and molecular studies showed that a novel fungus Equicapillimyces hongkongensis gen. nov., sp. nov. is the most likely cause of this syndrome. It is a septate branching hyaline mould which grows optimally at 30°C, requires nicotinic acid but is inhibited by cycloheximide, and specifically infects horse hair. Hyphae fill the core of infected hair shafts with short-necked structures resembling ascomata containing banana-shaped septate ascospore-like structures perforating th...
Time-dependent changes of cytokines mRNA in bronchoalveolar lavage fluid from symptomatic recurrent airway obstruction-affected horses. During an 18 day test, we measured the cytokine mRNA expression (Interleukin-1beta [IL-1beta], Interleukin-8 [IL-8], Interferon-gamma [IFN-gamma], Tumor Necrosis Factor-alpha [TNF-alpha]) of cells from bronchoalveolar lavage fluid [BALF] in five horses previously diagnosed with RAO, before and during challenge exposure, and after the desensitization phase which involved dexamethasone treatment and environmental modification. Simultaneously, the same cytokine mRNA expression of cells from BALF in four asymptomatic RAO-affected horses maintained outdoors was analyzed. An evident respiratory dist...
In vitro characterization of EHV-4 gG-deleted mutant. Equine herpesvirus 4 (EHV-4) is an important pathogen that causes respiratory tract disease in horse populations worldwide. Glycoprotein G (gG) homologs have been identified in several alphaherpesviruses as minor non-essential membrane-anchored glycoproteins. In this study, EHV-4 gG deletion mutant has been generated by using bacterial artificial chromosome technology to investigate the role of gG in viral pathogenesis. Our findings reported here revealed no significant difference between parental EHV-4 and gG-negative strain in their replication cycle in cell culture. Furthermore, virus titer...
Hypoxia regulates the expression of extracellular matrix associated proteins in equine dermal fibroblasts via HIF1. 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...
A preliminary study of Salmonella, verocytotoxigenic Escherichia coli/Escherichia coli O157 and Campylobacter on four mixed farms. The aims of this study were to investigate the incidence of Salmonella, verocytotoxigenic Escherichia coli (VTEC)/Escherichia coli O157 and Campylobacter on four mixed farms and to characterize the isolates in terms of a range of virulence factors. Eighty-nine composite (five different samples from the same animal species combined) faecal [cattle (24), pigs (14), sheep (4), poultry (4), horses (7), deer (4), dogs (9), rodents (2) and wild birds (20)] samples, 16 composite soil samples plus 35 individual water samples were screened using culture-based, immunomagnetic separation and molecular me...
Mapping B-cell epitopes in equine rhinitis B viruses and identification of a neutralising site in the VP1 C-terminus. Erbovirus is a genus of the family Picornaviridae and equine rhinitis B virus (ERBV) is the sole species. Erboviruses infect horses causing acute respiratory disease and sub-clinical and persistent infections. Despite the high seroprevalence and worldwide distribution of these viruses, the pathogenesis and antigenic structure of the three ERBV serotypes (ERBV1, 2 and 3) is poorly understood. To characterise linear epitopes on ERBV structural proteins, a set of fusion proteins were expressed in Escherichia coli. These proteins were tested in Western blot and ELISA and reactive proteins were als...
Equine recurrent uveitis: classification, etiology, and pathogenesis. Equine recurrent uveitis is a cyclical disease that affects the eye and often leads to high management costs and unfavorable results, such as blindness. Research has improved understanding of the roles of various etiologies, especially leptospirosis, in initiating and perpetuating the pathogenesis of equine recurrent uveitis. Research has also led to the discovery that specific breeds and horses with specific coat color patterns may be predisposed to developing recurrent uveitis.
The steroid catabolic pathway of the intracellular pathogen Rhodococcus equi is important for pathogenesis and a target for vaccine development. Rhodococcus equi causes fatal pyogranulomatous pneumonia in foals and immunocompromised animals and humans. Despite its importance, there is currently no effective vaccine against the disease. The actinobacteria R. equi and the human pathogen Mycobacterium tuberculosis are related, and both cause pulmonary diseases. Recently, we have shown that essential steps in the cholesterol catabolic pathway are involved in the pathogenicity of M. tuberculosis. Bioinformatic analysis revealed the presence of a similar cholesterol catabolic gene cluster in R. equi. Orthologs of predicted M. tuberculosis vi...
Behaviour of equine influenza virus in a naïve population: a practitioner’s perspective. We describe the behaviour of equine influenza (EI) virus infection in a naïve population as observed by equine veterinary practitioners. The clinical signs displayed by infected horses and the highly contagious nature of the disease are discussed, as well as the treatment and management of infected horses.
Equine amnionitis and fetal loss: mare abortion following experimental exposure to Processionary caterpillars (Ochrogaster lunifer). In Australia, there have been recent reports of unusual abortions in mid- to late-gestation mares. These were clinically distinct from other recognised causes of pregnancy loss and the term 'equine amnionitis and fetal loss' (EAFL) was adopted to describe this syndrome. Initial investigations concluded that possible causal factors included the presence on affected stud farms of Processionary caterpillars (Ochrogaster lunifer). Objective: To determine if exposure of pregnant mares to Processionary caterpillars or their shed exoskeletons can induce EAFL. Methods: Processionary caterpillars and t...
Evaluation of infectivity of a canine lineage H3N8 influenza A virus in ponies and in primary equine respiratory epithelial cells. To evaluate whether an equine-derived canine H3N8 influenza A virus was capable of infecting and transmitting disease to ponies. Methods: 20 influenza virus-seronegative 12- to 24-month-old ponies. Methods: 5 ponies were inoculated via aerosol exposure with 10(7) TCID(50) of A/Canine/Wyoming/86033/07 virus (Ca/WY)/pony. A second group of 5 ponies (positive control group) was inoculated via aerosol exposure with a contemporary A/Eq/Colorado/10/07 virus (Eq/CO), and 4 sham-inoculated ponies served as a negative control group. To evaluate the potential for virus transmission, ponies (3/inoculatio...
Identification of functional domains of the IR2 protein of equine herpesvirus 1 required for inhibition of viral gene expression and replication. 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...
Chondrocyte apoptosis determined by caspase-3 expression varies with fibronectin distribution in equine articular cartilage. The purpose of this study was to investigate associations between the extent of chondrocyte apoptosis and expression of the articular cartilage (AC) extracellular matrix (ECM) molecules, cartilage oligomeric matrix protein (COMP) and fibronectin. Methods: Cartilage from four sites (when available) on equine left middle carpal joints (n = 12) were used. Expression of COMP and fibronectin was determined using specific polyclonal antibodies and a biotin-streptavidin/peroxidase method. The intensity of staining for matrix molecules was graded (none, mild, moderate, strong) in each cartilage zone. ...
Upregulation of equine matrix metalloproteinase 1 by bovine papillomavirus type 1 is through the transcription factor activator protein-1. 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) activity is necessary for the transformation phenotype of equine fibroblasts. Among the many changes induced by BPV-1, matrix metalloproteinase 1 (MMP-1) upregulation contributes to the invasiveness of equine fibroblasts. However, it is not yet known how BPV-1 proteins regulate equine MMP-1 expression. To elucidate this mechanism, the equine MMP-1 prom...
The pathogenic and vaccine strains of equine infectious anemia virus differentially induce cytokine and chemokine expression and apoptosis in macrophages. The attenuated equine infectious anemia virus (EIAV) vaccine was the first attenuated lentivirus vaccine to be used in a large-scale application and has been used to successfully control the spread of equine infectious anemia (EIA) in China. To better understand the potential role of cytokines in the pathogenesis of EIAV infection and resulting immune response, we used branched DNA technology to compare the mRNA expression levels of 12 cytokines and chemokines, including IL-1α, IL-1β, IL-4, IL-10, TNF-α, IFN-γ, IP-10, IL-8, MIP-1α, MIP-1β, MCP-1, and MCP-2, in equine monocyte-derived mac...
Decreased infectivity of a neutralization-resistant equine infectious anemia virus variant can be overcome by efficient cell-to-cell spread. Two variants of equine infectious anemia virus (EIAV) that differed in sensitivity to broadly neutralizing antibody were tested in direct competition assays. No differences were observed in the growth curves and relative fitness scores of EIAVs of principal neutralizing domain variants of groups 1 (EIAV(PND-1)) and 5 (EIAV(PND-5)), respectively; however, the neutralization-resistant EIAV(PND-5) variant was less infectious in single-round replication assays. Infectious center assays indicated similar rates of cell-to-cell spread, which was approximately 1,000-fold more efficient than cell-free ...
Equine influenza: a clinical perspective in Centennial Parklands Equestrian Centre. The clinical signs of horses diagnosed with equine influenza (EI) at Centennial Parklands Equestrian Centre (CPEC) and the events surrounding their diagnosis are described. This was the site of the first case of EI diagnosed outside of the Eastern Creek Animal Quarantine Station. The clinical data demonstrate the rapid spread of the disease after a sufficient viral load had developed from the initial cases within CPEC.
The SnSAG merozoite surface antigens of Sarcocystis neurona are expressed differentially during the bradyzoite and sporozoite life cycle stages. Sarcocystis neurona is a two-host coccidian parasite whose complex life cycle progresses through multiple developmental stages differing at morphological and molecular levels. The S. neurona merozoite surface is covered by multiple, related glycosylphosphatidylinositol-linked proteins, which are orthologous to the surface antigen (SAG)/SAG1-related sequence (SRS) gene family of Toxoplasma gondii. Expression of the SAG/SRS proteins in T. gondii and another related parasite Neospora caninum is life-cycle stage specific and seems necessary for parasite transmission and persistence of infection. I...
Infection of peripheral blood mononuclear cells with neuropathogenic equine herpesvirus type-1 strain Ab4 reveals intact interferon-α induction and induces suppression of anti-inflammatory interleukin-10 responses in comparison to other viral strains. The recent increase in incidence, morbidity, and mortality of neurological disease induced by equine herpesvirus type 1 (EHV-1) has suggested a change of virulence of the virus. The exact mechanisms by which EHV-1 induces neurologic disease are not known. Environmental, viral, and host risk factors might contribute to neurological manifestation. Here, we investigated innate interferon-α (IFN-α), interleukin-10 (IL-10) and IL-4 responses after infection of equine peripheral blood mononuclear cells (PBMC) with EHV-1 using an available cytokine multiplex assay. Three viral strains representing ...
Association of Streptococcus equi with equine monocytes. Streptococcus equi (Se), the cause of equine strangles, is highly resistant to phagocytosis by neutrophils and is usually classified as an extracellular pathogen. Large numbers of the organism in tonsillar tissues during the acute phase of the disease are completely eliminated during convalescence by mechanisms not yet understood. In this study we demonstrate in an opsono-bactericidal assay and by cytometry and confocal microscopy that Se is interiorized and killed by equine blood monocytes. This finding supports the hypotheses that adaptive immune clearance is mediated by tonsillar macrophage...
Coll2-1, Coll2-1NO2 and myeloperoxidase concentrations in the synovial fluid of equine tarsocrural joints affected with osteochondrosis. The measurement of biomarkers that reflect cartilage breakdown is a powerful tool for investigating joint damage caused by disease or injury. Particularly in cases of osteochondrosis, synovial concentrations of these biomarkers may reveal the presence of osteoarthritic changes. Coll2-1, Coll2-1 NO2 and myeloperoxidase have recently been introduced in equine osteoarticular research but comparison between the concentrations of these markers in OCD affected and healthy joints has not been made. Therefore, this study aimed at reporting the synovial concentrations of these biomarkers in joints affe...
Vulvar epithelioid hemangiosarcoma with solar elastosis in a mare. A 15-year-old female gray Appaloosa horse was presented with history of a mass over the right dorsal commissure of vulva for the past 7 months. Based on histopathological examination, and positive staining with factor VIII-related antigen, vimentin, and Verhoeff-van Gieson stain, the vulvar mass was diagnosed as hemangiosarcoma with marked solar elastosis.
