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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.
Repeated emergence of epidemic/epizootic Venezuelan equine encephalitis from a single genotype of enzootic subtype ID virus. Venezuelan equine encephalitis (VEE) epidemics and equine epizootics occurred periodically in the Americas from the 1920s until the early 1970s, when the causative viruses, subtypes IAB and IC, were postulated to have become extinct. Recent outbreaks in Columbia and Venezuela have renewed interest in the source of epidemic/epizootic viruses and their mechanism of interepizootic maintenance. We performed phylogenetic analyses of VEE virus isolates spanning the entire temporal and geographic range of strains available, using 857-nucleotide reverse transcription-PCR products including the E3 and ...
Equine dyschondroplasia (osteochondrosis)–histological findings and type VI collagen localization. This study describes (1) the histological appearance of dyschondroplasia, the primary lesion of osteochondrosis, in articular cartilage of the horse and (2) the localization of type VI collagen which is an important constituent of the extracellular matrix (ECM). Dyschondroplastic cartilage was identified on the basis of the presence of cartilage cores (i.e., cartilage extending into the subchondral bone) and confirmed with subsequent histological examination. Full-thickness cartilage samples from 57 horses were collected and paraffin embedded. Histological examination was used to examine the n...
Disruption of sphingolipid metabolism and induction of equine leukoencephalomalacia by Fusarium proliferatum culture material containing fumonisin B(2) or B(3). Fumonisin B(1), B(2), and B(3) are inhibitors of ceramide synthase, a key enzyme in the pathway for de novo sphingolipid biosynthesis. Corn, naturally contaminated with either predominantly fumonisin B(1) or pure fumonisin B(1), has been shown to cause equine leukoencephalomalacia (ELEM). It has been hypothesized that fumonisin-induced disruption of sphingolipid metabolism is an early event in the development of ELEM. Recently, it was shown that Fusarium proliferatum corn culture diets containing predominantly fumonisin B(2), but not diets which were predominantly fumonisin B(3), at 75 ppm (0....
Pathogenesis and virulence of Rhodococcus equi. Inhalation of the soil-borne organism, Rhodococcus equi, can lead to a chronic and severe pyogranulomatous pneumonia in young horses and immunocompromised people. In addition, ulcerative colitis is a common sequela to infection in foals, and dissemination from the lung to other body sites is not uncommon in either the horse or man. Although the facultative intracellular bacterium is susceptible to neutrophil-mediated killing, it is able to resist innate macrophage defenses and establish residence within the intracellular environment of that phagocyte. Definitive virulence factors of R. equi ha...
Acute colitis in adult horses. A review with emphasis on aetiology and pathogenesis. This review article describes the different aetiological agents known or suspected to cause colitis in the adult horse, namely Salmonella spp., Clostridium spp., Ehrlichia risticii, Cyathostomes, fungi, various antibiotics, drugs, and toxins, with emphasis on their mechanism of action. For each of the infectious agents, diagnostic procedures are indicated. The effects of endotoxin can be important in all forms of equine colitis.
Tumor necrosis factor-alpha production and disease severity after immunization with enriched major core protein (p26) and/or infection with equine infectious anemia virus. Cardinal features of equine infectious anemia (EIA) include fever, hemolytic anemia and thrombocytopenia during the acute phase of the disease, and cachexia and anemia seen during the chronic phase. These signs are thought to result from the release of inflammatory cytokines such as TNF-alpha. In order to determine if TNF-alpha has a role in the pathogenesis of acute EIA and vaccine-induced disease enhancement, we measured plasma concentrations of TNF-alpha in ponies immunized with virus enriched major core protein-p26 and/or experimentally infected with EIAV. Naturally infected inapparent EIA...
Agonist-induced adherence of equine eosinophils to fibronectin. Eosinophils are believed to play an important part in the pathogenesis of equine diseases such as helminth infestation and the allergic skin disease, sweet itch. It has been shown that adherence of human eosinophils to the connective tissue matrix protein fibronectin enhances cell activation and survival time. If adherence causes similar changes in the properties of equine eosinophils, cell-induced tissue damage at a site of parasitic infestation or allergic response would be exacerbated. However, investigation of this hypothesis requires identification of mediators that cause equine eosinophi...
Herpesviral abortion in domestic animals. Abortion or neonatal disease may follow infection with several alpha, beta and gamma-herpesviruses. The alpha-herpesvirus, equid herpesvirus-1 (EHV-1), causes single or epizootic abortions or neonatal deaths in equids, and the closely related virus EHV-4 causes sporadic equine abortions. In cattle, the alpha-herpesviruses, bovine herpesvirus-1 (infectious bovine rhinotracheitis virus) and bovine herpesvirus-5 (bovine encephalitis virus), and a gamma-herpesvirus, bovine herpesvirus-4, have all been implicated as causes of abortion. In pigs, suid herpesvirus-1 (SHV-1: pseudorabies virus), an alp...
Control of equine infectious anemia virus is not dependent on ADCC mediating antibodies. Horses infected with equine infectious anemia virus (EIAV) have recurrent episodes of viremia which are eventually controlled, but the immune mechanisms have not been identified. Antibodies were detected to the surface of EIAV-infected cells within 1 month postinfection and remained for at least 3.5 years postinfection. These antibodies recognized cell surface-exposed envelope (Env) glycoproteins, but could not mediate antibody dependent cellular cytotoxicity (ADCC) using EIAV-WSU5-infected equine kidney (EK) cells as targets and peripheral blood mononuclear cells (PBMC) or polymorphonuclear c...
A novel family of viral death effector domain-containing molecules that inhibit both CD-95- and tumor necrosis factor receptor-1-induced apoptosis. Molluscum contagiosum virus proteins MC159 and MC160 and the equine herpesvirus 2 protein E8 share substantial homology to the death effector domain present in the adaptor molecule Fas-associated death domain protein (FADD) and the initiating death protease FADD-like interleukin-1beta-converting enzyme (FLICE) (caspase-8). FADD and FLICE participate in generating the death signal from both tumor necrosis factor receptor-1 (TNFR-1) and the CD-95 receptor. The flow of death signals from TNFR-1 occurs through the adaptor molecule tumor necrosis factor receptor-associated death domain protein (TRA...
Chronic exertional rhabdomyolysis. This article presents a brief description of what is known about the cause and pathogenesis of chronic intermittent rhabdomyolysis in horses. Clinically applicable diagnostic tests and published results in affected horses, prophylaxis, and treatment of the acute case are discussed.
Study of the duration and distribution of equine influenza virus subtype 2 (H3N8) antigens in experimentally infected ponies in vivo. The purpose of this experiment was to study the duration and distribution of equine influenza virus in actively infected ponies over a 3 wk period. Pony foals (6-8 mo old) were infected experimentally by nebulizing equine influenza subtype-2 virus ultrasonically through a face mask. Successful infection was clinically apparent as each of the foals (n = 6) had a febrile response, a deep hacking cough and mucopurulent nasal discharge for 7 to 10 d. The virus was isolated from nasopharyngeal swabs of all the ponies 3 and 5 d after infection and all the ponies seroconverted to the virus. Samples w...
Transforming growth factor-beta induced by live or ultraviolet-inactivated equid herpes virus type-1 mediates immunosuppression in the horse. Up to 21 days after exposure to live or ultraviolet-inactivated equid herpesvirus type-1 (EHV-1) autologous serum from ponies caused an immunosuppressive effect if incorporated into T-cell proliferation assays to EHV-1. The suppressive factor in the sera of ponies also inhibited T-cell response to phytohaemagglutinin. Increased levels of circulating activated transforming growth factor-beta 1 (TGF-beta 1) were detected, and the suppressive activity of the serum could be reversed by antibody to TGF-beta 1. In a challenge experiment the ponies which exhibited circulating TGF-beta 1 activity succ...
Identification of noncytopathic equine rhinovirus 1 as a cause of acute febrile respiratory disease in horses. Equine rhinovirus 1 (ERhV1) is a recognized cause of acute febrile respiratory disease in horse, although the virus is rarely isolated from such animals, despite seroprevalence rates as high as 50% in some horse populations. Recently, ERhV1 has been shown to be most closely related to foot-and-mouth disease virus, raising questions as to its disease associations in horses. We report that ERhV1 infection was the likely cause of two separate outbreaks of severe febrile respiratory disease which involved more than 20 horses. Attempts to isolate ErhV1 from nasopharyngeal swabs by conventional cell...
Oxidant injury, nitric oxide and pulmonary vascular function: implications for the exercising horse. The athletic ability of the horse is facilitated by vital physiological adaptations to high-intensity exercise, including a thin (but strong) pulmonary blood-gas barrier, a large pulmonary functional reserve capacity and a consequent maximum oxygen uptake (VO2max) far higher than in other species. A high pulmonary artery pressure also serves to enhance pulmonary function, although stress failure of lung capillaries at high pulmonary transmural pressures, and the contribution of other factors which act in the exercising horse to increase pulmonary vascular tone, may lead to pathological or path...
Gelatinolytic activity in tracheal aspirates of horses with chronic obstructive pulmonary disease. The gelatinolytic activity in tracheal aspirates (TA) of horses with chronic obstructive pulmonary disease (COPD) was analyzed using SDS-PAGE-gelatin-gel electrophoresis (zymography) and compared to TAs from healthy controls. The 110-90 kD MMP-9 type gelatinase was high in symptomatic disease phases (permanent disease 0.46 +/- 0.15, p < 0.001; or intermittent disease 0.47 +/- 0.12, p < 0.001) compared to healthy controls (0.10 +/- 0.07). Similarly, the overall gelatinolytic activity, the activity in high-mw gelatinolytic bands (210-190 and 150 kD) and in proteolytically processed fragments in ...
Analysis of the long terminal repeat from a cytopathic strain of equine infectious anemia virus. Sequential passage of the tissue culture-adapted prototype strain of EIAV in fetal donkey dermal (FDD) cell cultures generated a virus stock which exhibits cytopathic effects in FDD cell cultures. In this study, the effects of the long terminal repeat (LTR) region on virus replication and cytopathogenicity were examined. The FDD-adapted virus LTR was found to contain a number of base pair mutations and a large insertion within the U3 region in comparison with the previously characterized LTR, lambda12. Transient gene expression studies showed that basal promoter activity, in FDD cell cultures,...
Effects of road transport on indices of stress in horses. Stress associated with road transport is believed to be a significant contributor to the pathogenesis of post transport respiratory disease in horses. To determine the effects of road transport on pulmonary function, pulmonary aerosol clearance rates were measured in 4 horses 24 h before, and immediately after, 24 h of road transport by delivering aerosolised 99mtechnetium-labelled diethylenetriaminepentacetate (99mTc-DTPA) to the lungs and monitoring its washout. Each horse was transported twice, once while the trailer was equipped with a leaf-spring suspension and bias-ply tyres (trailer's o...
Phorbol ester stimulation of equine macrophage cultures alters expression of equine infectious anemia virus. Equine infectious anemia virus (EIAV) is a lentivirus that replicates predominantly in mature tissue macrophages. Viral expression is strongly influenced by the state of differentiation of the host cell. While blood monocytes can be infected, viral transcription is limited until the cell differentiates into a mature macrophage. Activation of mature macrophages infected with EIAV might also alter viral expression, presumably through binding of cellular transcription factors to viral nucleic acid sequences within the long terminal repeat (LTR). Using DNA amplification techniques, we compared LTR...
Experimental contact of bighorn sheep (Ovis canadensis) with horses and cattle, and comparison of neutrophil sensitivity to Pasteurella haemolytica cytotoxins. Peripheral blood neutrophils from horses, cattle, and Rocky Mountain bighorn sheep (Ovis canadensis canadensis) were evaluated for susceptibility to cytotoxin-dependent lysis of different biotypes and serotypes of Pasteurella haemolytica of domestic sheep, cattle, bighorn sheep, or mountain goat (Oreamnos americana) origin utilizing a cytotoxicity assay which measures the degree of bacteria cytotoxin-killing of neutrophils. All isolates of P. haemolytica (biotypes A and T) were noncytotoxic to horse neutrophils. Thirteen of 18 R haemolytica biotype A isolates were cytotoxic (> 50% neutrophi...
Effects of ozone and airway inflammation on glutathione status and iron homeostasis in the lungs of horses. To investigate the effects of ozone and airway inflammation on indices of oxidant injury in horses. Methods: 5 clinically normal horses and 25 horses referred for poor performance. Methods: Blood, tracheal wash, and bronchoalveolar lavage fluid samples were collected before and after ozone exposure (n = 5) or from clinical cases (n = 25), and were analyzed for reduced glutathione (GSH), glutathione disulfide (GSSG), and free and total iron (Fe) values. A scoring system (0 to 5) was used to assess airway inflammation on the basis of clinical signs and cytologic analysis of the tracheal wash and...
Effects of fusarium moniliforme isolates on tissue and serum sphingolipid concentrations in horses. Disruption in sphingolipid (SL) metabolism is a biomarker of exposure to fumonisins. The role of altered SL metabolism in the pathogenesis of fumonisin toxicoses is not understood. A 27-d feeding trial in horses compared the toxic effects of 3 strains of Fusarium moniliforme: RRC 415, cultured from corn in MS; AU 2/3, cultured from feed associated with clinical signs of duodenitis-proximal jejunitis (DPJ) in horses in AL; and MRC 826, cultured from corn in South Africa and shown to cause equine leukoencephalomalacia (ELEM). These were cultured on corn and diluted with clean corn and grain mixe...
Comparison of the deduced matrix and fusion protein sequences of equine morbillivirus with cognate genes of the Paramyxoviridae. The nucleotide sequence of the matrix protein of equine morbillivirus (EMV) was determined to be 1062 nucleotides and coded for a deduced protein of M(r) 40148 having a net charge of + 19 at neutral pH. The matrix protein gene was separated from the P and F genes by intercistronic regions of 546 and 469 nucleotides, respectively. The nucleotide sequence which coded for the F protein was 1641 nucleotides and coded for a deduced protein of 546 amino acids having an M(r) of 60,447 and a charge + 4 at neutral pH. Partial sequence information was also determined for the P/V proteins. M, P and F pro...
Genomic quasispecies associated with the initiation of infection and disease in ponies experimentally infected with equine infectious anemia virus. Equine infectious anemia virus (EIAV) provides a uniquely dynamic system in which to study the mechanism and role of genomic variation in lentiviral persistence and pathogenesis. We have used a Shetland pony model of infection to investigate the association of specific long terminal repeat (LTR) and env gene genomic sequences with the initiation of infection and the onset of disease. We analyzed viral RNA isolated from a pathogenic stock of virus (EIAV PV) and from plasma taken during the first disease episode from two ponies infected with EIAV PV. Overall sequence variation within gp90 was lo...
Elevation of serum G-CSF level in horses with transportation-induced fever. Levels of granulocyte-colony stimulating factor (G-CSF) in the blood of horses were measured before and after a long-distance transportation to clarify the pathogenesis of transportation-induced fever. The serum G-CSF level was measured by its ability to stimulate growth in a mouse myeloblastic cell line, NFS-60. Of 26 horses transported for a long distance, 9 had fever more than 39.0 degrees C during or after transportation. After transportation, the serum G-CSF level significantly increased in horses with transportation-induced fever but not in those without fever, and the serum G-CSF level ...
Inhibition of the protease activity in tracheobronchial aspirates of horses with chronic obstructive pulmonary disease. To clarify the role of proteolytic enzymes in the pathogenesis of chronic obstructive pulmonary disease (COPD) in horses, and to investigate new possibilities for treatment of this disease by interfering in the proteolytic process. Methods: Effect of antiproteolytic activity of selected protease inhibitors on tracheal aspirates was studied in vitro, and the inhibition profiles were compared with those of purified proteases. Methods: Respiratory tract secretions with antiproteolytic activity from 9 horses with COPD. Methods: Caseinolytic agar-diffusion assay. Results: The protease-inhibition pr...
Histopathological and immunofluorescent studies on transplacental infection in experimentally induced abortion by equine arteritis virus. Five pregnant mares, at between 6 and 8 months gestation, were experimentally infected with the Bucyrus strain of equine arteritis virus (EAV). Of the five mares, four aborted and one died. The pathogenesis of the abortions was studied, using histopathologic techniques, tissue immunofluorescence and virus isolation. Common microscopic lesions in the maternal reproductive organs indicated myometritis with a degeneration of the myocytes and an infiltration of the mononuclear cells. Epithelial cells of the endometrial gland showed sporadic degeneration. Lesions in the fetal tissue included an atr...
Detection of eastern equine encephalomyelitis virus RNA in formalin-fixed, paraffin-embedded tissues using DNA in situ hybridization. Eastern equine encephalomyelitis (F.EE) virus was detected in infected formalin-fixed horse and emu tissues and in infected chicken embryo fibroblasts. Results of in situ hybridization using a digoxigenin-labeled 40-base DNA probe complementary to a conserved region of the EEE virus RNA compared favorably with results of both virus isolation and serum neutralization tests. This technique may be useful for diagnosis of EEE virus infection in various animal species, especially when fresh tissues are not available for analysis, and also will provide a means for studying the involvement of alphavi...
