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.
Semik-Gurgul E, Szmatoła T, Gurgul A, Pawlina-Tyszko K, Gałuszka A, Pędziwiatr R, Witkowski M, Ząbek T.DNA methylation is a key mechanism in transcription regulation, and aberrant methylation is a common and important mechanism in tumor initiation, maintenance, and progression. To find genes that are aberrantly regulated by altered methylation in horse sarcoids, we used reduced representation bisulfite sequencing (RRBS) accompanied by RNA sequencing (RNA-Seq) for methylome (whole genome DNA methylation sequencing) and transcriptome profiling, respectively. We found that the DNA methylation level was generally lower in lesion samples than in controls. In the analyzed samples, a total of 14,692 d...
Black JB, Frampton AR.Equine herpesvirus type 1 (EHV-1) is a highly transmissible pathogen that leads to a variety of clinical disease outcomes in infected horses. A major sequela that can occur after an EHV-1 infection is a neurological disease termed equine herpesvirus myeloencephalopathy (EHM). Clinical manifestations of EHM include fever, ataxia, incontinence, and partial to full paralysis, which may ultimately lead to the euthanization of the infected horse. To develop an effective treatment strategy for EHM, it is critical that the specific virus-host interactions that lead to EHM be investigated so that safe...
Fukuda K, Mita H, Tamura N, Kuroda T, Kuwano A, Takahashi T, Sato F.Persistent synovitis damages the articular cartilage in horses. To evaluate the effectiveness of treatment for synovitis using a model induced by intra-articular administration of monoiodoacetic acid (MIA), it is necessary to identify inflammatory biomarkers characteristic of the MIA model. Synovitis was induced by administering MIA into the unilateral antebrachiocarpal joints of five horses, and saline was injected into the contralateral joints as a control on day 0. Clinical and ultrasonographic examinations and synovial fluid collection were performed on days 0, 1, 2, 7, 14, 21, 28, and 35....
O'Brien TJ, Hollinshead F, Goodrich LR.Osteoarthritis (OA) is a common joint disease affecting humans and horses, resulting in significant morbidity, financial expense, and loss of athletic use. While the pathogenesis is incompletely understood, inflammation is considered crucial in the development and progression of the disease. Mesenchymal stromal cells (MSCs) have received increasing scientific attention for their anti-inflammatory, immunomodulatory, and pro-regenerative effects. However, there are concerns about their ability to become a commercially available therapeutic. Extracellular vesicles (EVs) are now recognized to play...
Muñoz-Prieto A, Contreras-Aguilar MD, Cerón JJ, Ayala de la Peña I, Martín-Cuervo M, Eckersall PD, Holm Henriksen IM, Tecles F, Hansen S.Equine gastric ulcer syndrome (EGUS) is a highly prevalent disease that affects horses worldwide. Within EGUS, two different forms have been described: equine squamous gastric disease (ESGD) and equine glandular gastric disease (EGGD). The associated clinical signs cause detrimental activity performance, reducing the quality of life of animals. Saliva can contain biomarkers for EGUS that could be potentially used as a complementary tool for diagnosis. The objective of this work was to evaluate the measurements of calprotectin (CALP) and aldolase in the saliva of horses as potential biomarkers ...
Moss A, Leise B, Hackett E.Laminitis is a complex and debilitating disease of horses. Numerous predisposing factors contribute to laminitis development, however the exact pathogenesis remains undetermined. Serum T4, cortisol, and histamine are components of the innate stress response and could play a causative or contributory role. Stress hormone concentrations in laminitis are largely unknown. Objective: To evaluate parameters associated with stress response in horses with laminitis, and compare these to healthy horses and horses with gastrointestinal (GI) disease. Methods: Thirty-eight adult horses presenting for non-...
Jindra C, Hainisch EK, Brandt S.Horses and other equid species are frequently affected by bovine papillomavirus type 1 and/or 2 (BPV1, BPV2)-induced skin tumors termed sarcoids. Although sarcoids do not metastasize, they constitute a serious health problem due to their BPV1/2-mediated resistance to treatment and propensity to recrudesce in a more severe, multiple form following accidental or iatrogenic trauma. This review provides an overview on BPV1/2 infection and associated immune escape in the equid host and presents early and recent immunotherapeutic approaches in sarcoid management.
Hansen S, Otten ND, Spang-Hanssen L, Bendorff C, Jacobsen S.Studies in people have found neutrophil gelatinase-associated lipocalin (NGAL) concentrations are increased in asthma and can be used to distinguish between asthma subtypes. NGAL has not yet been investigated in equine asthma (EA). Objective: To investigate the ability of NGAL concentrations in bronchoalveolar lavage (BAL) fluid and serum to distinguish between control horses, horses with mild-moderate EA (MEA) and horses with severe EA (SEA). Methods: Retrospective cross-sectional study. Methods: Details of endoscopic examination including tracheal mucus score (TMS, scale 0-5) and BAL cytolog...
Elliott J, Bailey SR.Equine laminitis has both fascinated and frustrated veterinary researchers and clinicians for many years. The recognition that many ponies suffering from pasture-associated laminitis have an insulin-dysregulated phenotype (endocrinopathic laminitis, EL) and that prolonged insulin and glucose infusions can experimentally induce laminar pathology and functional failure are seminal discoveries in this field. Researchers have studied the molecular basis for disease pathogenesis in models of EL, sepsis-related laminitis and supporting limb laminitis and generated much data over the last 15 years....
Mustonen AM, Lehmonen N, Paakkonen T, Raekallio M, Käkelä R, Niemelä T, Mykkänen A, Sihvo SP, Nieminen P.Individual fatty acids (FAs) and their derivatives (lipid mediators) with pro-inflammatory or dual anti-inflammatory and pro-resolving properties have potential to influence the health of joint tissues. Osteoarthritis (OA) is an age-associated chronic joint disease that can be featured with altered FA composition in the synovial fluid (SF) of human patients. The counts and cargo of extracellular vesicles (EVs), membrane-bound particles released by synovial joint cells and transporting bioactive lipids, can also be modified by OA. The detailed FA signatures of SF and its EVs have remained unexp...
Keller LE, Tait Wojno ED, Begum L, Fortier LA.Infiltration of cluster of differentiation (CD) 3 (CD3) T cells into the synovium and synovial fluid occurs in most patients with posttraumatic osteoarthritis. During disease progression, proinflammatory T helper 17 cells and anti-inflammatory regulatory T cells infiltrate the joint in response to inflammation. This study aimed to characterize the dynamics of regulatory T and T helper 17 cell populations in synovial fluid from equine clinical patients with posttraumatic osteoarthritis to determine whether phenotype and function are associated with potential immunotherapeutic targets. An imbala...
Karamendin K, Abishov A, Kydyrmanov A, Akhmetzhanova M.In 2011, there was an outbreak of a disease with mass abortions among horses in southeastern Kazakhstan. The AK-2011 strain was isolated from an aborted fetus and subsequently identified as equid alphaherpesvirus 1. Here, we describe the nearly complete genome sequence of the AK-2011 strain, attenuated for vaccine development.
Paraschou G, Vogel PE, Lee AM, Trawford RF, Priestnall SL.Multisystemic eosinophilic epitheliotropic disease (MEED) is a rare condition of equids characterized by eosinophilic infiltration of multiple organs. Clinical signs are variable depending on the affected organs. The most common clinical signs include chronic weight loss, diarrhoea and exfoliative dermatitis. Respiratory distress and raised liver enzymes are less frequently seen. The cause is unknown and the pathogenesis is poorly understood. There are less than 50 reported cases of horses with MEED. We now document the lesions in three donkeys with fluctuating or chronic loss of weight, letha...
Amaral A, Cebola N, Szóstek-Mioduchowska A, Rebordão MR, Kordowitzki P, Skarzynski D, Ferreira-Dias G.Myeloperoxidase is an enzyme released by neutrophils when neutrophil extracellular traps (NETs) are formed. Besides myeloperoxidase activity against pathogens, it was also linked to many diseases, including inflammatory and fibrotic ones. Endometrosis is a fibrotic disease of the mare endometrium, with a large impact on their fertility, where myeloperoxidase was shown to induce fibrosis. Noscapine is an alkaloid with a low toxicity, that has been studied as an anti-cancer drug, and more recently as an anti-fibrotic molecule. This work aims to evaluate noscapine inhibition of collagen type 1 (C...
Alshahrani SH, Alameri AA, Kahar F, Alexis Ramírez-Coronel A, Fadhel Obaid R, Alsaikhan F, Zabibah RS, Qasim QA, Altalbawy FMA, Fakri Mustafa Y....Recently in vivo and in vitro studies have provided evidence establishing the significance of microRNAs (miRNAs) in both physiological and pathological conditions. In this regard, the role of miRNA-128 (miR-128) in health and diseases has been found, and its critical regulatory role in the context of some viral diseases has been recently identified. For instance, it has been found that miR-128 can serve as an antiviral mediator and significantly limit the replication and dissemination of human immunodeficiency virus type 1 (HIV-1). Besides, it has been noted that poliovirus receptor-related 4 ...
Kuttappan DA, Mooyottu S, Sponseller BA.The understanding of the pathogenesis of equine enteric clostridial organisms is an active, evolving field. Advances will improve our knowledge both from the animal welfare and human health perspectives. The zoonotic nature of this group of diseases makes them relevant in the age of One health, as a significant amount of close human-equine interactions occurs for business and pleasure. Economic and welfare reasons prompt a better understanding of enteric clostridial pathogenesis, treatment, and control of the infection in horses and ongoing efforts are needed to advance clinical outcomes.
Dobiáš R, Jahn P, Tóthová K, Dobešová O, Višňovská D, Patil R, Škríba A, Jaworská P, Škorič M, Podojil L, Kantorová M, Mrázek J....Invasive pulmonary aspergillosis (IPA) may be a rare cause of granulomatous pneumonia in horses. The mortality of IPA is almost 100%; direct diagnostic tools in horses are needed. Bronchoalveolar lavage fluid (BALF) and serum samples were collected from 18 horses, including individuals suffering from IPA (n = 1), equine asthma (EA, n = 12), and 5 healthy controls. Serum samples were collected from another 6 healthy controls. Samples of BALF (n = 18) were analyzed for spp. DNA, fungal galactomannan (GM), ferricrocin (Fc), triacetylfusarinin C (TafC), and gliotoxin (Gtx). Analysis of 24 serum s...
Ochi A, Bannai H, Aonuma H, Kanuka H, Uchida-Fujii E, Kinoshita Y, Ohta M, Kambayashi Y, Tsujimura K, Ueno T, Nemoto M.Mosquitoes and EDTA-treated blood samples from febrile racehorses were investigated for Getah virus infection from 2016 to 2019 at the Miho Training Center, where several outbreaks of Getah virus have occurred. We collected 5557 mosquitoes and 331 blood samples from febrile horses in this study. The most frequently captured mosquito species was Culex tritaeniorhynchus (51.9%), followed by Aedes vexans nipponii (14.2%) and Anopheles sinensis (11.2%). Getah virus was detected in mosquitoes (Aedes vexans nipponii) in 2016 (strain 16-0810-26) but not in 2017-2019. Six of 74 febrile horses in 2016 ...
Bone reportsJanuary 5, 2023
Volume 18 101653 doi: 10.1016/j.bonr.2023.101653
Grissom SK, Semevolos SA, Duesterdieck-Zellmer K.The objective of this study is to better understand the pathogenesis of early equine osteochondrosis (OC) by identifying differences in gene and protein expression of extracellular matrix components and regulators in normal and diseased cartilage and bone, focusing on the osteochondral junction and cells surrounding the cartilage canals. We expected to find an upregulation of matrix metalloproteinases and a decrease in extracellular matrix constituent expression along the osteochondral junction and cells surrounding the cartilage canals in OC samples. Paraffin-embedded osteochondral samples (6...
Jacobsen S, Mortensen CD, Høj EA, Vinther AM, Berg LC, Adler DMT, Verwilghen D, van Galen G.Neutrophil gelatinase-associated lipocalin (NGAL) has been suggested to be a highly sensitive and specific marker of joint infection in humans. The aim of the study was to investigate NGAL concentrations in synovial fluid (SF) from horses with septic synovitis, horses without septic synovitis, and horses with uncertain status. NGAL was measured in 177 admission samples obtained from 152 horses. From a subset of horses ( = 35), additional samples obtained sequentially over the course of treatment were available. Concentrations of NGAL were significantly higher in septic synovitis ( = 47 samples...
Padoan E, Ferraresso S, Pegolo S, Barnini C, Castagnaro M, Bargelloni L.Mild equine asthma (MEA) and severe equine asthma (SEA) are two of the most frequent equine airway inflammatory diseases, but knowledge about their pathogenesis is limited. The goal of this study was to investigate gene expression differences in the respiratory tract of MEA- and SEA-affected horses and their relationship with clinical signs. Methods: Clinical examination and endoscopy were performed in 8 SEA- and 10 MEA-affected horses and 7 healthy controls. Cytological and microbiological analyses of bronchoalveolar lavage (BAL) fluid were performed. Gene expression profiling of BAL fluid wa...
Stoeckle SD, Timmermann D, Merle R, Gehlen H.Laminitic horses commonly suffer from an endocrine disease such as equine metabolic syndrome. Hyperinsulinemia is considered a key factor in the pathogenesis of laminitis. Since insulin also affects protein turnover in the body, the resting plasma amino acid concentrations of obese horses that were presented for a combined glucose insulin test (CGIT) were determined. In total, 25 obese horses and two lean horses with recurrent laminitis underwent a CGIT. Of these, five were not insulin dysregulated (obese), 14 were insulin dysregulated (ID), and eight were insulin-dysregulated and laminitic (I...
Wyler M, Sage SE, Marti E, White S, Gerber V.The diagnostic value of allergen-specific immunoglobulin E (IgE) in horses with asthma is uncertain. A recently developed protein microarray detected abnormally high latex-specific IgE concentrations in the serum of horses with severe asthma. Objective: The main objective was to characterize the IgE profiles of asthmatic horses in Switzerland using a protein microarray platform in serum and bronchoalveolar lavage fluid (BALF). The secondary objective was to determine whether serological and BALF allergen-specific IgE concentrations correlated. Methods: Forty-four asthmatic and 39 control horse...
Hainisch EK, Jindra C, Reicher P, Miglinci L, Brodesser DM, Brandt S.Equine sarcoids are common, locally aggressive skin tumors induced by bovine papillomavirus types 1, 2, and possibly 13 (BPV1, BPV2, BPV13). Current in vitro models do not mimic de novo infection. We established primary fibroblasts from horse skin and succeeded in infecting these cells with native BPV1 and BPV2 virions. Subsequent cell characterization was carried out by cell culture, immunological, and molecular biological techniques. Infection of fibroblasts with serial 10-fold virion dilutions (2 × 10-20 virions) uniformly led to DNA loads settling at around 150 copies/cell after four pass...
Akula S, Riihimäki M, Waern I, Åbrink M, Raine A, Hellman L, Wernersson S.Asthma is a chronic inflammatory airway disease and a serious health problem in horses as well as in humans. In humans and mice, mast cells (MCs) are known to be directly involved in asthma pathology and subtypes of MCs accumulate in different lung and airway compartments. The role and phenotype of MCs in equine asthma has not been well documented, although an accumulation of MCs in bronchoalveolar lavage fluid (BALF) is frequently seen. To characterize the phenotype of airway MCs in equine asthma we here developed a protocol, based on MACS Tyto sorting, resulting in the isolation of 92.9% pur...
Sanclemente JL, Rivera-Velez SM, Horohov DW, Dasgupta N, Sanz MG.Foals that develop pulmonary ultrasonographic lesions on Rhodococcus equi (R. equi) endemic farms are treated with antibiotics because those at risk of developing clinical pneumonia (~20%) cannot be recognised early. Candidate biomarkers identified using metabolomics may aid targeted treatment strategies against R. equi. Objective: (1) To describe how foal ageing affects their plasma metabolome (birth to 8 weeks) and (2) to establish the effects that experimental infection with Rhodococcus equi (R. equi) has on foal metabolome. Methods: Experimental study. Methods: Nine healthy newborn foals...
Mainguy-Seers S, Beaudry F, Fernandez-Prada C, Martin JG, Lavoie JP.Extracellular vesicles (EVs) contribute to intercellular communication through the transfer of their rich cargo to recipient cells. The EVs produced by LPS-stimulated neutrophils from healthy humans and horses increase airway smooth muscle (ASM) proliferation, but the roles of neutrophil EVs in asthma are largely unexplored. The aim of this study was to determine whether neutrophil-derived EVs isolated during the remission or exacerbation of asthma influence ASM proliferation differentially. Peripheral blood neutrophils were collected during remission and exacerbation in eight horses affected ...
Mustonen AM, Lehmonen N, Oikari S, Capra J, Raekallio M, Mykkänen A, Paakkonen T, Rilla K, Niemelä T, Nieminen P.Osteoarthritis (OA) is a degenerative joint disease with inadequately understood pathogenesis leading to pain and functional limitations. Extracellular vesicles (EVs) released by synovial joint cells can induce both pro- and anti-OA effects. Hyaluronic acid (HA) lubricates the surfaces of articular cartilage and is one of the bioactive molecules transported by EVs. In humans, altered EV counts and composition can be observed in OA synovial fluid (SF), while EV research is in early stages in the horse-a well-recognized OA model. The aim was to characterize SF EVs and their HA cargo in 19 horses...
Schliewert EC, Hooijberg EH, Steyn JS, Potgieter C, Fosgate GT, Goddard A.African Horse Sickness (AHS) is a vector-borne disease endemic to sub-Saharan Africa caused by African Horse Sickness Virus (AHVS). Infections in naïve horses have high morbidity and mortality rates. AHS pathogenesis is not well understood; neither the hematologic changes nor acute phase response occurring during infection has been fully evaluated. The study's objective was to characterize the hematologic changes and acute phase response during experimental infection with AHSV. Methods: 4 horses negative for AHSV group-specific antibodies. Methods: In this prospective, longitudinal study cond...
Ahearne MM, Pentzke-Lemus LL, Romano AM, Larsen ED, Watson AM, O'Fallon EA, Landolt GA.Equine influenza virus is a common cause of respiratory disease in equids. Few reports describe clinical presentation and disease progression in donkeys. Objective: Describe the clinical and diagnostic findings, outcome, and pathologic lesions associated with influenza pneumonia in donkeys. Methods: Thirteen unvaccinated donkeys ranging from 1 week to 12 years of age and sharing clinical signs and exposure history. Methods: Retrospective case series. Medical records from June to July 2020 at the Colorado State Veterinary Teaching Hospital and collaborating referring veterinary practices wer...
Grieder FB, Vogel SN.To investigate the role of type I interferon (IFN) and its regulatory transacting proteins, interferon regulatory factors (IRF-1 and IRF-2), in early protection against infection with virulent Venezuelan equine encephalitis virus (VEE), we utilized mice with targeted mutations in the IFN-alpha/beta receptor, IRF-1, or IRF-2 genes. IFN-alpha/beta-receptor knockout mice are highly susceptible to peripheral infection with virulent or attenuated VEE, resulting in their death within 24 and 48 h, respectively. Treatment of normal macrophages with anti-IFN-alpha/beta antibody prior to and during infe...
von Bargen K, Haas A.The soil actinomycete Rhodococcus equi is a pulmonary pathogen of young horses and AIDS patients. As a facultative intracellular bacterium, R. equi survives and multiplies in macrophages and establishes its specific niche inside the host cell. Recent research into chromosomal virulence factors and into the role of virulence plasmids in infection and host tropism has presented novel aspects of R. equi infection biology and pathogenicity. This review will focus on new findings in R. equi biology, the trafficking of R. equi-containing vacuoles inside host cells, factors involved in virulence and ...
Patterson-Kane JC, Becker DL, Rich T.The equine superficial digital flexor tendon (SDFT) is a frequently injured structure that is functionally and clinically equivalent to the human Achilles tendon (AT). Both act as critical energy-storage systems during high-speed locomotion and can accumulate exercise- and age-related microdamage that predisposes to rupture during normal activity. Significant advances in understanding of the biology and pathology of exercise-induced tendon injury have occurred through comparative studies of equine digital tendons with varying functions and injury susceptibilities. Due to the limitations of in-...
Richter PJ, Kimsey RB, Madigan JE, Barlough JE, Dumler JS, Brooks DL.Ehrlichia equi, a rickettsia described from horses in California 30 yr ago, causes equine granulocytic ehrlichiosis throughout the Americas and possibly Europe. Here, we report experimental transmission of E. equi from infected to susceptible horses through bites of western blacklegged ticks, Ixodes pacificus (Cooley & Kohls). In preliminary field studies, only I. pacificus consistently infested horses and vegetation at 3 locations with contemporary cases of equine ehrlichosis, and in particular, I. pacificus was the only species found attached to all of the infected horses. Exposure to bites ...
Giguère S, Cohen ND, Chaffin MK, Hines SA, Hondalus MK, Prescott JF, Slovis NM.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.
Powers AM, Oberste MS, Brault AC, Rico-Hesse R, Schmura SM, Smith JF, Kang W, Sweeney WP, Weaver SC.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 ...
Scheel TK, Kapoor A, Nishiuchi E, Brock KV, Yu Y, Andrus L, Gu M, Renshaw RW, Dubovi EJ, McDonough SP, Van de Walle GR, Lipkin WI, Divers TJ....Nonprimate hepacivirus (NPHV) is the closest known relative of hepatitis C virus (HCV) and its study could enrich our understanding of HCV evolution, immunity, and pathogenesis. High seropositivity is found in horses worldwide with ∼ 3% viremic. NPHV natural history and molecular virology remain largely unexplored, however. Here, we show that NPHV, like HCV, can cause persistent infection for over a decade, with high titers and negative strand RNA in the liver. NPHV is a near-universal contaminant of commercial horse sera for cell culture. The complete NPHV 3'-UTR was determined and consists...
Pirie RS.Recurrent airway obstruction is a widely recognised airway disorder, characterised by hypersensitivity-mediated neutrophilic airway inflammation and lower airway obstruction in a subpopulation of horses when exposed to suboptimal environments high in airborne organic dust. Over the past decade, numerous studies have further advanced our understanding of different aspects of the disease. These include clarification of the important inhaled airborne agents responsible for disease induction, improving our understanding of the underlying genetic basis of disease susceptibility and unveiling the fu...
Vannella KM, Moore BB.Idiopathic pulmonary fibrosis (IPF) remains exactly that. The disease originates from an unknown cause, and little is known about the mechanisms of pathogenesis. While the disease is likely multi-factorial, evidence is accumulating to implicate viruses as co-factors (either as initiating or exacerbating agents) of fibrotic lung disease. This review summarizes the available clinical and experimental observations that form the basis for the hypothesis that viral infections may augment fibrotic responses. We review the data suggesting a link between hepatitis C virus, adenovirus, human cytomegalo...
Boyle AG, Timoney JF, Newton JR, Hines MT, Waller AS, Buchanan BR.This consensus statement update reflects our current published knowledge and opinion about clinical signs, pathogenesis, epidemiology, treatment, complications, and control of strangles. This updated statement emphasizes varying presentations in the context of existing underlying immunity and carrier states of strangles in the transmission of disease. The statement redefines the "gold standard" for detection of possible infection and reviews the new technologies available in polymerase chain reaction diagnosis and serology and their use in outbreak control and prevention. We reiterate the impo...
Prokhorov NS, Riccio C, Zdorovenko EL, Shneider MM, Browning C, Knirel YA, Leiman PG, Letarov AV.Bacteriophages recognize and bind to their hosts with the help of receptor-binding proteins (RBPs) that emanate from the phage particle in the form of fibers or tailspikes. RBPs show a great variability in their shapes, sizes, and location on the particle. Some RBPs are known to depolymerize surface polysaccharides of the host while others show no enzymatic activity. Here we report that both RBPs of podovirus G7C - tailspikes gp63.1 and gp66 - are essential for infection of its natural host bacterium E. coli 4s that populates the equine intestinal tract. We characterize the structure and funct...
Venter M, Swanepoel R.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...
Dubey JP, Lindsay DS, Saville WJ, Reed SM, Granstrom DE, Speer CA.Equine protozoal myeloencephalitis (EPM) is a serious neurological disease of horses in the Americas. The protozoan most commonly associated with EPM is Sarcocystis neurona. The complete life cycle of S. neurona is unknown, including its natural intermediate host that harbors its sarcocyst. Opossums (Didelphis virginiana, Didelphis albiventris) are its definitive hosts. Horses are considered its aberrant hosts because only schizonts and merozoites (no sarcocysts) are found in horses. EPM-like disease occurs in a variety of mammals including cats, mink, raccoons, skunks, Pacific harbor seals, p...
Venter M, Human S, Zaayman D, Gerdes GH, Williams J, Steyl J, Leman PA, Paweska JT, Setzkorn H, Rous G, Murray S, Parker R, Donnellan C, Swanepoel R.Serologic evidence suggests that West Nile virus (WNV) is widely distributed in horses in southern Africa. However, because few neurologic cases have been reported, endemic lineage 2 strains were postulated to be nonpathogenic in horses. Recent evidence suggests that highly neuroinvasive lineage 2 strains exist in humans and mice. To determine whether neurologic cases are being missed in South Africa, we tested 80 serum or brain specimens from horses with unexplained fever (n = 48) and/or neurologic signs (n = 32) for WNV. From March 2007 through June 2008, using reverse transcription-PCR (RT-...
Bowen RA, Nemeth NM.West Nile virus emerged recently in North America as a serious human and animal pathogen. This review summarizes the use of experimental infections with West Nile virus in diverse vertebrate species that have been used to answer fundamental questions about the host response, pathogenesis of West Nile virus infection and virus evolution. Results: West Nile virus has an extremely broad vertebrate host range. Infection of common species of birds has defined those with high vs. low potential to serve as amplifying hosts for the virus. In general, mammals (primates, horses, companion animals) are d...
Shirato K, Kimura T, Mizutani T, Kariwa H, Takashima I.West Nile (WN) virus is a mosquito-borne flavivirus that can cause lethal encephalitis in humans and horses. The WN virus endemic in New York City (NY) in 1999 caused large-scale mortality of wild birds that was not evident in endemic areas in other parts of the world, and the pathogenesis of the WN virus strain isolated in NY (NY strain) appears to differ from that of previously isolated strains. However, the pathogenesis of NY strain infection remains unclear. This study examined CC (RANTES/CCL5, MIP-1 alpha/CCL3, MIP-1 beta/CCL4) and CXC (IP-10/CXCL10, B lymphocyte chemoattractant (BLC/CXCL...
Corning S.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...
Hornig M, Briese T, Licinio J, Khabbaz RF, Altshuler LL, Potkin SG, Schwemmle M, Siemetzki U, Mintz J, Honkavuori K, Kraemer HC, Egan MF, Whybrow PC....In 1983, reports of antibodies in subjects with major depressive disorder (MDD) to an as-yet uncharacterized infectious agent associated with meningoencephalitis in horses and sheep led to molecular cloning of the genome of a novel, negative-stranded neurotropic virus, Borna disease virus (BDV). This advance has enabled the development of new diagnostic assays, including in situ hybridization, PCR and serology based on recombinant proteins. Since these assays were first implemented in 1990, more than 80 studies have reported an association between BDV and a wide range of human illnesses that i...
Fernandes F, Chen K, Ehrlich LS, Jin J, Chen MH, Medina GN, Symons M, Montelaro R, Donaldson J, Tjandra N, Carter CA.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...
van der Geize R, Grommen AW, Hessels GI, Jacobs AA, Dijkhuizen L.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...
Fridell RA, Partin KM, Carpenter S, Cullen BR.Several members of the lentivirus family of complex retroviruses have been shown to encode proteins that are functionally equivalent to the Rev posttranscriptional regulatory protein of human immunodeficiency virus type 1 (HIV-1). Furthermore, the domain organization of HIV-1 Rev, featuring a highly basic N-terminal RNA binding domain and a leucin-rich C-terminal effector domain, has also been shown to be highly conserved among Rev proteins derived from not only the primate but also the ovine and caprine lentiviruses. Although it has therefore appeared highly probable that the lentivirus equin...
Habarugira G, Suen WW, Hobson-Peters J, Hall RA, Bielefeldt-Ohmann H.West Nile virus (WNV) is an important zoonotic flavivirus responsible for mild fever to severe, lethal neuroinvasive disease in humans, horses, birds, and other wildlife species. Since its discovery, WNV has caused multiple human and animal disease outbreaks in all continents, except Antarctica. Infections are associated with economic losses, mainly due to the cost of treatment of infected patients, control programmes, and loss of animals and animal products. The pathogenesis of WNV has been extensively investigated in natural hosts as well as in several animal models, including rodents, lagom...
Bian J, Khaychuk V, Angers RC, Fernández-Borges N, Vidal E, Meyerett-Reid C, Kim S, Calvi CL, Bartz JC, Hoover EA, Agrimi U, Richt JA, Castilla J....Adaptation of prions to new species is thought to reflect the capacity of the host-encoded cellular form of the prion protein (PrP) to selectively propagate optimized prion conformations from larger ensembles generated in the species of origin. Here we describe an alternate replicative process, termed nonadaptive prion amplification (NAPA), in which dominant conformers bypass this requirement during particular interspecies transmissions. To model susceptibility of horses to prions, we produced transgenic (Tg) mice expressing cognate PrP Although disease transmission to only a subset of infecte...
Schaffartzik A, Hamza E, Janda J, Crameri R, Marti E, Rhyner C.Insect bite hypersensitivity (IBH) is an allergic dermatitis of the horse caused by bites of insects of the genus Culicoides and is currently the best characterized allergic disease of horses. This article reviews knowledge of the immunopathogenesis of IBH, with a particular focus on the causative allergens. Whereas so far hardly any research has been done on the role of antigen presenting cells in the pathogenesis of IBH, recent studies suggest that IBH is characterized by an imbalance between a T helper 2 (Th2) and regulatory T cell (T(reg)) immune response, as shown both locally in the skin...
Kono Y, Hirasawa K, Fukunaga Y, Taniguchi T.Horses which had passed a few months to a few years asymptomatically after the last recurrence of equine infectious anemia (EIA) showed a typical febrile response after treatment with the immunosuppressive agent, dexamethasone (DM) or cyclophosphamide (CY). In horses showing a febrile response, EIA virus which had not been neutralized by neutralizing antibody previously produced was propagated. In DM-treated horses it disappeared from the blood soon after pyretolysis and antibody against the virus was produced promptly. In contrast, detectable viremia persisted in CY-treated horses for 10 to 8...
Baer A, Lundberg L, Swales D, Waybright N, Pinkham C, Dinman JD, Jacobs JL, Kehn-Hall K.Venezuelan equine encephalitis virus (VEEV) is a previously weaponized arthropod-borne virus responsible for causing acute and fatal encephalitis in animal and human hosts. The increased circulation and spread in the Americas of VEEV and other encephalitic arboviruses, such as eastern equine encephalitis virus and West Nile virus, underscore the need for research aimed at characterizing the pathogenesis of viral encephalomyelitis for the development of novel medical countermeasures. The host-pathogen dynamics of VEEV Trinidad donkey-infected human astrocytoma U87MG cells were determined by car...
Fielding CL, Higgins JK, Higgins JC, McIntosh S, Scott E, Giannitti F, Mete A, Pusterla N.Equine coronavirus (ECoV) is associated with clinical disease in adult horses. Outbreaks are associated with a low case fatality rate and a small number of animals with signs of encephalopathic disease are described. Objective: The aim of this study is to describe the epidemiological and clinical features of two outbreaks of ECoV infection that were associated with an high case fatality rate. Methods: 14 miniature horses and 1 miniature donkey testing fecal positive for ECoV from two related disease outbreaks. Methods: Retrospective study describing the epidemiological findings, clinicopatholo...
Karikoski NP, McGowan CM, Singer ER, Asplin KE, Tulamo RM, Patterson-Kane JC.Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of laminitis, with hyperinsulinemia playing a key role. Descriptions of laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were ...
Olstad K, Hendrickson EH, Carlson CS, Ekman S, Dolvik NI.To transect blood vessels within epiphyseal cartilage canals and observe whether this resulted in ischaemic chondronecrosis, an associated focal delay in enchondral ossification [osteochondrosis (OC)] and pathological cartilage fracture [osteochondrosis dissecans (OCD)] in the distal femur of foals, with potential translational value to the pathogenesis of juvenile osteochondritis dissecans (JOCD) in children. Methods: Ten Norwegian Fjord Pony foals were operated at the age of 13-15 days. Two vessels supplying the epiphyseal growth cartilage of the lateral trochlear ridge of the left distal fe...
Pirie RS, Collie DD, Dixon PM, McGorum BC.Equine heaves is a naturally occurring organic dust-induced asthma characterized by airway neutrophilia, mucus hypersecretion and obstructive lung dysfunction. However, the relative role of different dust components in disease severity remains unclear. Objective: This study investigated the relative contribution of inhaled endotoxin and organic dust particulates (mainly mould spores) in inducing heaves in heaves-susceptible horses. Methods: Control and heaves-susceptible horses received inhalation challenges with hay dust suspension (HDS) before and after lipopolysaccharide (LPS) depletion. He...
