The equine immune system is a complex network of cells, tissues, and organs that work collaboratively to defend against pathogens and maintain homeostasis. It consists of innate and adaptive components, each with distinct functions and mechanisms. The innate immune system provides the first line of defense through physical barriers, phagocytic cells, and the complement system. The adaptive immune system involves lymphocytes, such as B cells and T cells, which generate specific responses to antigens and provide immunological memory. Research in equine immunology explores the interactions between these components, the impact of genetic and environmental factors on immune function, and the development of vaccines and therapeutics. This page gathers peer-reviewed studies and scholarly articles focusing on the mechanisms, regulation, and clinical applications of the equine immune system in health and disease.
Brandt S.Sarcoids are benign, yet locally aggressive skin tumours that commonly affect horses and other equid species. The lesions are induced by bovine papillomavirus types 1, 2, and probably 13 in conjunction with other factors including trauma and a genetic predisposition. Although sarcoids have a substantial impact on the health and welfare of affected equids, information on the immune response to bovine papillomavirus infection and resulting sarcoids is limited. However, there is evidence that sarcoid disease is associated with an impaired immune response to bovine papillomavirus infection. This o...
Veit M, Matczuk AK.Equine arteritis virus (EAV) is a positive-stranded RNA virus of the Arteriviridae family. Its GP5/M dimer, the principal component of the viral envelope, mediates virus budding and serves as a key target for neutralizing antibodies. Using AlphaFold3, we predicted the 3D structure of the EAV GP5/M dimer and compared it to its homolog in porcine reproductive and respiratory syndrome virus (PRRSV). Both complexes share a conserved architecture comprising a short ectodomain, three helical transmembrane regions, and a β-sheet-rich endodomain. EAV GP5 features a longer ectodomain with four α-heli...
van den Brom-Spierenburg AJ, Siegers EW, Westermann CM, Vernooij JCM, Sloet van Oldruitenborgh-Oosterbaan MM, Theelen MJP.In hospitalized foals, limited data are available on the utility of sequential measurement of SAA concentrations and the value of these data in a clinical setting. Objective: To determine serum amyloid A (SAA) concentrations in ill neonatal foals at multiple timepoints during hospitalization, and to evaluate a potential association with systemic inflammatory response syndrome (SIRS) status, blood culture (BC) result, and survival. Methods: Hospitalized ill foals (n = 90, ≤ 14 days). Methods: In this retrospective study, foals were classified based on SIRS criteria: "SIRS" or "NonSIRS," ...
McKenna KD, Struble SE, Max LNF, Linardi RL, Ortved KF.To quantify platelets, leukocytes, cytokines, and growth factors in ProVet autologous platelet concentrate (APC). We hypothesized that APC would contain significantly increased leukocytes and platelets compared to whole blood and significantly increased concentrations of anti-inflammatory cytokines and growth factors compared to serum. Unassigned: Blood was obtained from 6 horses and processed to produce APC. Leukocyte and platelet concentrations were quantified in whole blood and APC. Cytokines, including interleukin (IL)-1β, IL-4, IL-6, IL-10, tumor necrosis factor-α, and IL-1Ra, and growt...
Dörsam K, Nischang V, Büttner K, Fey K, Werz O, Jordan PM.Equine asthma (EA) is a chronic inflammatory disease of the lower respiratory tract in horses, which is mainly triggered by dusty hay. EA is becoming increasingly acknowledged as a valuable animal model for studying human asthma. Research on the pathogenesis of EA has primarily focused on the associated cells and cytokines involved. However, the role of inflammation-related lipid mediators (LM) in the development and progression of equine asthma remains elusive. LMs are categorized into pro-inflammatory arachidonic acid (AA)-derived leukotrienes (LTs) and prostaglandins (PGs), as well as infla...
Conrad NL, Mazzoleni I, Abreu MC, Costa AV, Di Giácomo CP, Zorzi VSG, Leite FPL.Equine proliferative enteropathy (EPE), caused by Lawsonia intracellularis induces intestinal epithelial hyperplasia, resulting in malabsorption, weight loss, colic, and diarrhea. Despite its clinical and economic importance, no equine-specific vaccine is commercially available. Recombinant subunit vaccines are a safe and scalable alternative; however, their immunogenicity often requires improvement. Probiotic supplementation with Bacillus toyonensis may act as an immunomodulatory strategy to potentiate vaccine efficacy. This study aimed to evaluate the immunogenicity of a recombinant protein ...
Dillmann JB, Dos Santos TS, Dos Santos RC, Monteiro SG.Equine cutaneous pythiosis, caused by Pythium insidiosum, is a severe disease in tropical and subtropical regions, often leading to progressive granulomatous lesions with poor response to conventional therapies. Standard treatment includes surgical excision and immunotherapy, but recurrence is common, particularly in distal limb lesions. Maggot Debridement Therapy (MDT) with disinfected Lucilia cuprina larvae provides selective debridement, microbial control, and stimulation of granulation, representing a potential adjunctive option. This report describes the successful use of MDT combined wit...
Wójtowicz A, Sadowska A, Myszczyński K, Molcan T, Kaczmarek MM, Szóstek-Mioduchowska A.Fibrosis remains incompletely understood, particularly in terms of how immune mediators shape stromal programs. We used a spontaneous large‑animal model-endometrosis (equine endometrial fibrosis) to define how interleukin‑4 (IL‑4) reprograms fibroblasts from healthy and fibrotic endometrium. Primary fibroblasts were exposed to IL‑4 (10 ng/mL) for 48 or 96 h. At 48 h, bulk transcriptomes revealed 1307 differentially expressed genes (DEGs; 648 up, 659 down) and 1271 DEGs (645 up, 626 down) in fibroblasts derived from endometria without or with endometrosis, respectively. Enrichment an...
Acevedo-Jiménez GE, Morales-González C, Akbarin MM, Rodríguez-Murillo C, González-Fernández VD, Avila-De la Vega LM, García-Flores MM....Equine infectious anemia virus (EIAV) is a globally significant equine pathogen, and its control relies on effective serological surveillance. The agar gel immunodiffusion (AGID) test, the WOAH-prescribed method, has limitations in sensitivity. This study developed and validated an indirect ELISA using a synthetic peptide derived from a conserved region of the EIAV gp90 surface glycoprotein. The assay was evaluated using 773 horse sera from the Metropolitan Zone of the Valley of Mexico and compared to the AGID test. The gp90-EIAV ELISA demonstrated a sensitivity of 85.3 % and a specificity o...
Toddy T, Ledbetter EC, Knickelbein KE.To describe the demographics and treatment outcomes of horses definitively diagnosed with epithelial or stromal immune-mediated keratitis (IMMK) by use of in vivo confocal microscopy (IVCM) and/or histopathology. Unassigned: Medical records of horses presented to the Cornell University Equine Hospital definitively diagnosed with epithelial or stromal IMMK with IVCM and/or histopathology between 2020 and 2024 were reviewed. Patient signalment, affected eye(s), diagnostics, treatments, and outcomes were assessed. Unassigned: 22 horses met the inclusion criteria. The mean age was 16.9 years (SD, ...
Bartenschlager F, Kuropka B, Schmitz P, Dumke F, Landmann K, Gruber AD, Weise C, Schnabel CL, Gehlen H, Mundhenk L.Mucus hypersecretion and accumulation are hallmark features of equine asthma (EA), a meaningful respiratory disorder in horses occurring in mild to moderate (MEA) and severe (SEA) forms. Changes of the proteomic composition of airway mucus in EA are poorly understood. Using label-free quantitative liquid chromatography-mass spectrometry, we analyzed airway mucus from SEA (n = 10), MEA (n = 6), and healthy (n = 8) horses. We identified and quantified 2,275 proteins including gel-forming mucins MUC5AC and MUC5B and membrane-bound mucins MUC1 and MUC4. Compared with healthy controls, ...
von der Höden FJ, Stefansdottir SB, Torsteinsdottir S, Svansson V, Björnsson JM, Wagner B, Mahmuti D, Marti E, Jonsdottir S.Insect bite hypersensitivity (IBH) is a seasonal, IgE-mediated allergic dermatitis of horses caused by salivary gland proteins of biting midges ( spp.). Current management relies on relief of clinical signs and on physical protection. In a previous pilot study, healthy horses were fed transgenic barley expressing a allergen via a special spiral bit, which successfully induced allergen-specific antibody responses. Building on this concept, the present study aimed to evaluate a more practical feeding approach, delivering transgenic barley expressing the major allergen Cul o 2p in a feed-compat...
Verstraete MH, Norris JK, Loux SC, De Spiegelaere W, Carossino M, Daels P, Dini P.The placenta mediates critical interactions between mother and offspring that guide development and impact long-term health. Despite its importance, the cellular organization of the equine (Equus caballus) placenta remains poorly defined. The equine epitheliochorial placenta, characterized by the absence of trophoblast invasion and prominent endocrine activity, provides a unique comparative model for studying placental cellular composition and development. Methods: We applied single-cell RNA sequencing to chorioallantois tissue collected from first-trimester (n = 1) and term (n = 2) equine...
Böckmann S, Trzebiatowski L, Georgiev P, Büttner K, Wehrend A.Immunoglobulins ingested via colostrum must remain intact to be absorbed by the neonate. Equine colostrum contains antitrypsin activity, which likely protects these proteins from proteolysis in the gastrointestinal tract. Objective: To quantify antitrypsin activity in equine colostrum and milk, describe its temporal changes during the first five days after parturition, compare actitvity between left and right mammary glands, evaluate differences between nulliparous and pluriparous mares, and examine associations with immunoglobulin G (IgG) concentrations and mare age. Methods: This retrospecti...
Young KAS, Schnabel LV, Gilger BC.Equine ocular disease is common and often challenging to treat using traditional methods. This has led to the development of new therapies. Like human medicine, veterinary medicine is adopting cellular and gene therapy as innovative approaches. Equine ocular disease is a particularly promising area for these techniques. Notably, immune-mediated diseases (such as immune-mediated keratitis and equine recurrent uveitis), ulcerative keratitis, and infectious ocular diseases are of interest. Several ocular gene therapy products are approved for use in humans, and more are currently being researched...
Li Z, Yu T, Ge L, Lv S, Fu Q, Shi H.Equine herpesvirus type 1 (EHV-1) is a major veterinary pathogen causing significant economic losses in the livestock industry. Despite its impact, effective vaccines and targeted antiviral strategies remain limited, largely due to an incomplete understanding of host factors regulating viral replication and pathogenesis. Unassigned: To systematically identify host genes essential for EHV-1 infection, we established a BHK-21 cell line stably expressing Cas9 and performed a genome-wide CRISPR/Cas9 knockout screen using a pooled lentiviral single-guide RNA library. Significantly enriched candidat...
Dropsy H, Husson JC, Degorce-Rubiales F, Cochet-Faivre N.A 9-year-old gelding Quarter Horse with a lesion on the right upper eyelid was diagnosed with cutaneous lupus erythematosus. Clinical resolution and control of UV-induced flares were achieved with topical tacrolimus and a UV-blocking mask without adverse effects over the following 3 years.
Aucoin AA, Zhidkov V, Legere RM, Borba KER, Landrock KK, Parker LE, Bray JM, Bordin AI, Cohen ND.To characterize age-related trajectories of the relative concentrations of anti-virulence-associated protein A (VapA) immunoglobulin (Ig)-G1, IgG3/5, IgG4/7, and IgA in serum and bronchoalveolar lavage fluid (BALF) as indicators of systemic and intrapulmonary immune responses in foals naturally exposed to Rhodococcus equi. Unassigned: Blood and BALF samples were collected at ages 4, 14, 28, and 56 days from healthy Quarter Horse foals (n = 19) naturally exposed to R equi. Samples were tested via ELISA for relative concentration of IgG1, IgG3/5, IgG4/7, and IgA recognizing the VapA of R equi. D...
Schmitz M, Neugebauer E, Full F, Conn KL.Comparative transcriptomics offers a powerful approach to elucidate host-virus interactions across related pathogens, yet systematic evaluations across species-matched cellular systems remain limited. We performed a cross-species RNA sequencing analysis of respective species' cells infected with three alphaherpesviruses-herpes simplex virus 1 (HSV-1), bovine alphaherpesvirus 1 (BHV-1), and equid alphaherpesvirus 1 (EHV-1)-to dissect conserved and virus-specific transcriptional responses. We show that certain orthologous genes and orthologous pathways are differentially regulated upon infection...
Carotenuto SE, Broussard G, Fox GA, Hayes WK.To assess the efficacy of a new equine F[ab'] antivenom (US Department of Agriculture code 6101.05) in removing serum venom and lowering the snakebite severity score (SSS) in animals suffering from naturally occurring viperid envenomation. Methods: Retrospective study, April 2020 to October 2021. Methods: Veterinary hospitals across four North American regions. Methods: Twenty-two dogs, one cat, and one horse. Methods: All patients received the new antivenom intravenously and were assessed for clinical response. Most dogs required one vial for clinical control of signs. Results: Among the dogs...
Pettersson J, Levanov L, Tervo S, Hautala K, Aaltonen K, Utriainen M, Kareinen L, Gadd T, Sironen T, Vapalahti O, Kinnunen PM.Parapoxviruses (PPV) cause skin and mucous membrane signs to several animal species and humans worldwide. Equine parapoxvirus (EqPPV) was first detected in a sick horse in Finland in 2013. It is potentially zoonotic, and a similar virus has been detected in humans in the USA. In winter 2021–2022, EqPPV caused a large-scale pastern dermatitis epidemic in racehorses all over Finland. Field reports suggest that similar epidemics of unverified cause have also occurred in 2015 and 2019. The aim of this study was to develop a serological test and study the immune response, seroprevalence, and hist...
Heilen LB, Roßgardt J, Dern-Wieloch J, Vogelsberg J, Staszyk C.Horses' hypsodont (high-crowned) teeth face permanent dental wear. This is compensated for by a continuous eruption, which requires a high adaptability of odontoblasts; otherwise, the dental pulp would be exposed. Here, we report on how equine odontoblasts respond to the challenge of maintaining a high production rate of dentin. We analyzed CD90, a marker of odontoblastic differentiation, and nestin, a marker of mature odontoblasts, in equine pulpal tissue via immunofluorescence. For comparison, we examined the hypselodont (ever-growing) incisors and brachydont (short-crowned) molars of rats. ...
Richardson LM, Gordon J, Davila C, Chamoun-Emanuelli AM, Zdyrski C, Whitfield-Cargile CM.Gastrointestinal (GI) disease is a major cause of morbidity and mortality in horses, with disruption of the intestinal epithelial barrier playing a central role in disease pathogenesis. A deeper understanding of the molecular and functional properties of the equine intestinal barrier is essential to improve diagnostics and therapeutics. While intestinal organoids have emerged as a promising tool for modeling GI physiology and disease, equine-specific data remain limited. Existing studies vary in methodology and often lack functional characterization, particularly across different intestinal re...
Thieulent CJ, Sarkar S, Carossino M, Bhowmik M, Zhu H, Balasuriya UBR.Our laboratory identified the susceptible allelic variant of equine CXCL16 protein (EqCXCL16S) as an entry receptor for equine arteritis virus (EAV). However, EAV has a broad host cell tropism and infects cells that lack EqCXCL16S. Thus, we hypothesized that EAV interacts with other host cell protein(s) that facilitate EAV infection. A virus overlay protein-binding assay in combination with a Far-Western blot from EAV-susceptible equine pulmonary artery endothelial cells (EECs) and equine dermal fibroblasts (E. Derm) identified a 57 kDa protein, present in the membrane fraction of the protein ...
Beniwal N, Lal B, Mithina S, Verma CK, Kumar S, Phagna V, Jakhar K, Sonar S, Gupta V, Singh R, Kumar N, Tan CW, Thachamvally R, Singha H, Murzello K....Rabies is a neglected tropical zoonotic disease caused by rabies-virus (RV) infection and is responsible for almost 60,000 annual deaths globally, largely affecting the socio-economically disadvantaged population. Although fatality is preventable by immunization either before or after exposure with therapeutic antibodies, the high cost of prophylaxis or treatment limits their accessibility for the affected population. However, due to the almost 100% fatality rate in symptomatic individuals, almost 29 million annual vaccinations are performed, imposing high financial burden. Human transmission ...
Shahid MA, Guitart AS, Bertin FR, Simon O, Ceusters J, Serteyn D, Whitworth DJ.A minimally invasive microbiopsy-based method for the isolation of mesenchymal stem cells (MSCs) from equine skeletal muscle (M-MSCs) provides a readily accessible source of MSCs for clinical applications. We examined the expression of genes associated with immunomodulation and anti-inflammatory pathways, in addition to those of growth factors and the major histocompatibility complex (MHC) molecules I and II, at constitutive levels and after priming with inflammatory cytokines, an immunostimulant, and heat-shocking. While there was notable variation between the M-MSCs from each of the horses i...
Varela V, Costa M, Maciel C, Barbeito J, Barrera EE, Gutierre E, Correa A, Elgue M, Carrasco S, Larrosa MD, Pereira M, Correa J, Crosignani N....Anti-NGF monoclonal antibodies have recently been approved for treating degenerative joint disease, including osteoarthritis pain, in dogs and cats. However, their widespread use is limited by high cost and the requirement for repeated injections. Nerve Growth Factor and Substance P play central roles in the initiation and maintenance of inflammation and chronic pain in OA. There is a pressing need for new, safe, cost-effective therapies that target the underlying mechanisms of OA chronic pain. Here, we designed and produced a novel recombinant fusion protein, termed rNGFSP, which functions as...
Kirmse L, Thieme K, Doherr MG, Eule JC.To evaluate different laboratory procedures for determining the etiologic diagnosis of equine recurrent uveitis regarding intraocular infection with Leptospira spp. and to establish a diagnostic guideline. Methods: Eighty horses with a history of ERU were ophthalmologically examined. Serum and aqueous humor were collected. Total protein, albumin level, and MAT against Leptospira spp. were evaluated on serum and aqueous humor. PCR for Leptospira spp., EHV-1 and -4 was performed on aqueous humor. Goldmann-Witmer coefficient (GWC) and C-value (CC) were calculated based on MAT. In 42 cases, an add...
Qiu Y, Lei Y, Yi X, Tang X, Zhang B, Wang S, Sun X.This study investigated three donkey breeds-Guanzhong, Jiami, and Northern Shaanxi-to characterize the structural organization and diversification mechanisms of the immunoglobulin light-chain (IgL) loci and to conduct both intra-breed and interspecies comparisons with horses. The donkey IGλ locus is located on chromosome 8 and arranged in a Vλ-(Jλ-Cλ)-Vλ configuration. It contains 7 Cλ genes, each preceded by a corresponding Jλ gene to form a Jλ-Cλ cluster. Upstream of this cluster, 156 Vλ genes were identified, including 29 potential functional genes; downstream, 98 Vλ genes were d...
Connor RJ, Kawaoka Y, Webster RG, Paulson JC.The receptor specificity of 56 H2 and H3 influenza virus isolates from various animal species has been determined to test the relevance of receptor specificity to the ecology of influenza virus. The results show that the receptor specificity of both H2 and H3 isolates evaluated for sialic acid linkage specificity and inhibition of hemagglutination by horse serum correlates with the species of origin, as postulated earlier for H3 strains based on a limited survey of five human, three avian, and one equine strain. Elucidation of the amino acid sequence of several human H2 receptor variants and a...
Suzuki Y, Ito T, Suzuki T, Holland RE, Chambers TM, Kiso M, Ishida H, Kawaoka Y.The distribution of sialic acid (SA) species varies among animal species, but the biological role of this variation is largely unknown. Influenza viruses differ in their ability to recognize SA-galactose (Gal) linkages, depending on the animal hosts from which they are isolated. For example, human viruses preferentially recognize SA linked to Gal by the alpha2,6(SAalpha2,6Gal) linkage, while equine viruses favor SAalpha2,3Gal. However, whether a difference in relative abundance of specific SA species (N-acetylneuraminic acid [NeuAc] and N-glycolylneuraminic acid [NeuGc]) among different animal...
Majorek KA, Porebski PJ, Dayal A, Zimmerman MD, Jablonska K, Stewart AJ, Chruszcz M, Minor W.Serum albumin (SA) is the most abundant plasma protein in mammals. SA is a multifunctional protein with extraordinary ligand binding capacity, making it a transporter molecule for a diverse range of metabolites, drugs, nutrients, metals and other molecules. Due to its ligand binding properties, albumins have wide clinical, pharmaceutical, and biochemical applications. Albumins are also allergenic, and exhibit a high degree of cross-reactivity due to significant sequence and structure similarity of SAs from different organisms. Here we present crystal structures of albumins from cattle (BSA), h...
den Boon JA, Snijder EJ, Chirnside ED, de Vries AA, Horzinek MC, Spaan WJ.The nucleotide sequence of the genome of equine arteritis virus (EAV) was determined from a set of overlapping cDNA clones and was found to contain eight open reading frames (ORFs). ORFs 2 through 7 are expressed from six 3'-coterminal subgenomic mRNAs, which are transcribed from the 3'-terminal quarter of the viral genome. A number of these ORFs are predicted to encode structural EAV proteins. The organization and expression of the 3' part of the EAV genome are remarkably similar to those of coronaviruses and toroviruses. The 5'-terminal three-quarters of the genome contain the putative EAV p...
Lykkesfeldt J, Svendsen O.Important infectious diseases in farm animals, such as pneumonia and enteritis, are thought to be associated with the so-called oxidative stress, i.e. a chemical phenomenon involving an imbalance in the redox status of the individual animal. The specifics of oxidative stress and how it may result in disease or be prevented are complex questions with no simple answers. However, the considerable literature on the subject suggests that many researchers consider oxidative stress-related mechanisms to be important early events in disease development. A particularly intriguing aspect is that, at lea...
Prescott JF.Recent isolations of Rhodococcus equi from cavitatory pulmonary disease in patients with AIDS have aroused interest among medical microbiologists in this unusual organism. Earlier isolations from humans had also been in immunosuppressed patients following hemolymphatic tumors or renal transplantation. This organism has been recognized for many years as a cause of a serious pyogranulomatous pneumonia of young foals and is occasionally isolated from granulomatous lesions in several other species, in some cases following immunosuppression. The last decade has seen many advances in understanding o...
Couëtil LL, Cardwell JM, Gerber V, Lavoie JP, Léguillette R, Richard EA.The purpose of this manuscript is to revise and update the previous consensus statement on inflammatory airway disease (IAD) in horses. Since 2007, a large number of scientific articles have been published on the topic and these new findings have led to a significant evolution of our understanding of IAD.
Quinlivan M, Zamarin D, García-Sastre A, Cullinane A, Chambers T, Palese P.Equine influenza is a common disease of the horse, causing significant morbidity worldwide. Here we describe the establishment of a plasmid-based reverse genetics system for equine influenza virus. Utilizing this system, we generated three mutant viruses encoding carboxy-terminally truncated NS1 proteins. We have previously shown that a recombinant human influenza virus lacking the NS1 gene (delNS1) could only replicate in interferon (IFN)-incompetent systems, suggesting that the NS1 protein is responsible for IFN antagonist activity. Contrary to previous findings with human influenza virus, w...
Pawelek KA, Huynh GT, Quinlivan M, Cullinane A, Rong L, Perelson AS.Influenza virus infection remains a public health problem worldwide. The mechanisms underlying viral control during an uncomplicated influenza virus infection are not fully understood. Here, we developed a mathematical model including both innate and adaptive immune responses to study the within-host dynamics of equine influenza virus infection in horses. By comparing modeling predictions with both interferon and viral kinetic data, we examined the relative roles of target cell availability, and innate and adaptive immune responses in controlling the virus. Our results show that the rapid and ...
Puffer BA, Parent LJ, Wills JW, Montelaro RC.We have previously demonstrated that the Gag p9 protein of equine infectious anemia virus (EIAV) is functionally homologous with Rous sarcoma virus (RSV) p2b and human immunodeficiency virus type 1 (HIV-1) p6 in providing a critical late assembly function in RSV Gag-mediated budding from transfected COS-1 cells (L. J. Parent et al., J. Virol. 69:5455-5460, 1995). In light of the absence of amino acid sequence homology between EIAV p9 and the functional homologs of RSV and HIV-1, we have now designed an EIAV Gag-mediated budding assay to define the late assembly (L) domain peptide sequences con...
Woldehiwet Z.Anaplasma phagocytophilum is the recently designated name replacing three species of granulocytic bacteria, Ehrlichia phagocytophila, Ehrlichia equi and the agent of human granulocytic ehrlichiosis, after the recent reorganization of the families Rickettsiaceae and Anaplasmataceae in the order Rickettsiales. Tick-borne fever (TBF), which is caused by the prototype of A. phagocytophilum, was first described in 1932 in Scotland. A similar disease caused by a related granulocytic agent was first described in horses in the USA in 1969; this was followed by the description of two distinct granulocy...
Burbelo PD, Dubovi EJ, Simmonds P, Medina JL, Henriquez JA, Mishra N, Wagner J, Tokarz R, Cullen JM, Iadarola MJ, Rice CM, Lipkin WI, Kapoor A.Genetic and biological characterization of new hepaciviruses infecting animals contributes to our understanding of the ultimate origins of hepatitis C virus (HCV) infection in humans and dramatically enhances our ability to study its pathogenesis using tractable animal models. Animal homologs of HCV include a recently discovered canine hepacivirus (CHV) and GB virus B (GBV-B), both viruses with largely undetermined natural host ranges. Here we used a versatile serology-based approach to determine the natural host of the only known nonprimate hepacivirus (NPHV), CHV, which is also the closest p...
Jahrling PB, Geisbert TW, Geisbert JB, Swearengen JR, Bray M, Jaax NK, Huggins JW, LeDuc JW, Peters CJ.A passive immunization strategy for treating Ebola virus infections was evaluated using BALB/ c mice, strain 13 guinea pigs, and cynomolgus monkeys. Guinea pigs were completely protected by injection of hyperimmune equine IgG when treatment was initiated early but not after viremia had developed. In contrast, mice were incompletely protected even when treatment was initiated on day 0, the day of virus inoculation. In monkeys treated with one dose of IgG on day 0, onset of illness and viremia was delayed, but all treated animals died. A second dose of IgG on day 5 had no additional beneficial e...
Hiemstra PS, Maassen RJ, Stolk J, Heinzel-Wieland R, Steffens GJ, Dijkman JH.Antileukoprotease (ALP), or secretory leukocyte proteinase inhibitor, is an endogenous inhibitor of serine proteinases that is present in various external secretions. ALP, one of the major inhibitors of serine proteinases present in the human lung, is a potent reversible inhibitor of elastase and, to a lesser extent, of cathepsin G. In equine neutrophils, an antimicrobial polypeptide that has some of the characteristics of ALP has been identified (M. A. Couto, S. S. L. Harwig, J. S. Cullor, J. P. Hughes, and R. I. Lehrer, Infect. Immun. 60:5042-5047, 1992). This report, together with the catio...
MacDonald GH, Johnston RE.The initial steps of Venezuelan equine encephalitis virus (VEE) spread from inoculation in the skin to the draining lymph node have been characterized. By using green fluorescent protein and immunocytochemistry, dendritic cells in the draining lymph node were determined to be the primary target of VEE infection in the first 48 h following inoculation. VEE viral replicon particles, which can undergo only one round of infection, identified Langerhans cells to be the initial set of cells infected by VEE directly following inoculation. These cells are resident dendritic cells in the skin, which mi...
de Vries AA, Chirnside ED, Horzinek MC, Rottier PJ.We have recently shown that the genome of equine arteritis virus (EAV) contains seven open reading frames (ORFs). We now present data on the structural proteins of EAV and the assignment of their respective genes. Virions are composed of a 14-kDa nucleocapsid protein (N) and three membrane proteins designated M, GS, and GL. M is an unglycosylated protein of 16 kDa, and GS and GL are N-glycosylated proteins of 25 and 30 to 42 kDa, respectively. The broad size distribution of GL results from heterogeneous N-acetyllactosamine addition since it is susceptible to digestion by endo-beta-galactosidas...
Pallister J, Middleton D, Wang LF, Klein R, Haining J, Robinson R, Yamada M, White J, Payne J, Feng YR, Chan YP, Broder CC.The henipaviruses, Hendra virus (HeV) and Nipah virus (NiV), are two deadly zoonotic viruses for which no vaccines or therapeutics have yet been approved for human or livestock use. In 14 outbreaks since 1994 HeV has been responsible for multiple fatalities in horses and humans, with all known human infections resulting from close contact with infected horses. A vaccine that prevents virus shedding in infected horses could interrupt the chain of transmission to humans and therefore prevent HeV disease in both. Here we characterise HeV infection in a ferret model and show that it closely mirror...
van Kasteren PB, Bailey-Elkin BA, James TW, Ninaber DK, Beugeling C, Khajehpour M, Snijder EJ, Mark BL, Kikkert M.Protein ubiquitination regulates important innate immune responses. The discovery of viruses encoding deubiquitinating enzymes (DUBs) suggests they remove ubiquitin to evade ubiquitin-dependent antiviral responses; however, this has never been conclusively demonstrated in virus-infected cells. Arteriviruses are economically important positive-stranded RNA viruses that encode an ovarian tumor (OTU) domain DUB known as papain-like protease 2 (PLP2). This enzyme is essential for arterivirus replication by cleaving a site within the viral replicase polyproteins and also removes ubiquitin from cell...
Hauck SM, Dietter J, Kramer RL, Hofmaier F, Zipplies JK, Amann B, Feuchtinger A, Deeg CA, Ueffing M.Autoimmune uveitis is a blinding disease presenting with autoantibodies against eye-specific proteins as well as autoagressive T cells invading and attacking the immune-privileged target tissue retina. The molecular events enabling T cells to invade and attack the tissue have remained elusive. Changes in membrane protein expression patterns between diseased and healthy stages are especially interesting because initiating events of disease will most likely occur at membranes. Since disease progression is accompanied with a break-down of the blood-retinal barrier, serum-derived proteins mask the...
Patel JR, Heldens J.This review concentrates on the epidemiology, latency and pathogenesis of, and the approaches taken to control infection of horses by equine herpesvirus types 1 (EHV-1) and 4 (EHV-4). Although both viruses may cause febrile rhinopneumonitis, EHV-1 is the main cause of abortions, paresis and neonatal foal deaths. The lesion central to these three conditions is necrotising vasculitis and thrombosis resulting from lytic infection of endothelial cells lining blood capillaries. The initiation of infection in these lesions is likely to be by reactivated EHV-1 from latently infected leukocytes. Howev...
Timoney JF.Streptococci pathogenic for the horse include S. equi (S. equi subsp. equi), S. zooepidemicus (S. equi subsp. zooepidemicus), S. dysgalactiae subsp. equisimilis and S. pneumoniae capsule Type III. S. equi is a clonal descendent or biovar of an ancestral S. zooepidemicus strain with which it shares greater than 98% DNA homology and therefore expresses many of the same proteins and virulence factors. Rapid progress has been made in identification of virulence factors and proteins uniquely expressed by S. equi. Most of these are expressed either on the bacterial surface or are secreted. Notable e...
Guy JS, Breslin JJ, Breuhaus B, Vivrette S, Smith LG.A coronavirus was isolated from feces of a diarrheic foal and serially propagated in human rectal adenocarcinoma (HRT-18) cells. Antigenic and genomic characterizations of the virus (isolate NC99) were based on serological comparison with other avian and mammalian coronaviruses and sequence analysis of the nucleocapsid (N) protein gene. Indirect fluorescent-antibody assay procedures and virus neutralization assays demonstrated a close antigenic relationship with bovine coronavirus (BCV) and porcine hemagglutinating encephalomyelitis virus (mammalian group 2 coronaviruses). Using previously des...
Snijder EJ, Wassenaar AL, Spaan WJ.To study the proteolytic processing of the equine arteritis virus (EAV) replicase open reading frame 1a (ORF1a) protein, specific antisera were raised in rabbits, with six synthetic peptides and a bacterial fusion protein as antigens. The processing of the EAV ORF1a product in infected cells was analyzed with Western blot (immunoblot) and immunoprecipitation techniques. Additional information was obtained from transient expression of ORF1a cDNA constructs. The 187-kDa ORF1a protein was found to be subject to at least five proteolytic cleavages. The processing scheme, which covers the entire OR...
Rogers GN, Pritchett TJ, Lane JL, Paulson JC.Human and animal (avian and equine) influenza A virus isolates of the H3 serotype exhibit marked differences in their ability to bind specific sialyloligosaccharide sequences that serve as cell surface receptor determinants (G. Rogers and J. Paulson, 1983, Virology 127, 361-373). Whereas human isolates of this subtype strongly agglutinate enzymatically modified human erythrocytes containing the terminal SA alpha 2,6Gal sequence, avian and equine isolates preferentially agglutinate erythrocytes bearing the SA alpha 2, 3Gal sequence. As shown in this report, a glycoprotein found in horse serum, ...
Dutkiewicz J, Mackiewicz B, Kinga Lemieszek M, Golec M, Milanowski J.Pantoea agglomerans, a bacterium associated with plants, is not an obligate infectious agent in humans. However, it could be a cause of opportunistic human infections, mostly by wound infection with plant material, or as a hospital-acquired infection, mostly in immunocompromised individuals. Wound infection with P. agglomerans usually follow piercing or laceration of skin with a plant thorn, wooden splinter or other plant material and subsequent inoculation of the plant-residing bacteria, mostly during performing of agricultural occupations and gardening, or children playing. Septic arthritis ...
Garmashova N, Atasheva S, Kang W, Weaver SC, Frolova E, Frolov I.The encephalitogenic New World alphaviruses, including Venezuelan (VEEV), eastern (EEEV), and western equine encephalitis viruses, constitute a continuing public health threat in the United States. They circulate in Central, South, and North America and have the ability to cause fatal disease in humans and in horses and other domestic animals. We recently demonstrated that these viruses have developed the ability to interfere with cellular transcription and use it as a means of downregulating a cellular antiviral response. The results of the present study suggest that the N-terminal, approxima...
Ewers C, Bethe A, Stamm I, Grobbel M, Kopp PA, Guerra B, Stubbe M, Doi Y, Zong Z, Kola A, Schaufler K, Semmler T, Fruth A, Wieler LH, Guenther S.To discern the relevance of ST648 extended-spectrum β-lactamase (ESBL)-producing Escherichia coli as a putative new group of multiresistant and extraintestinal pathogenic strains in animals, its frequency, ESBL types, antimicrobial resistance patterns and virulence gene (VG) profiles should be determined and compared with ST131 strains from the same collection of strains. Methods: ESBL-producing E. coli isolates (n = 1152), consecutively sampled from predominantly dogs, cats and horses between 2008 and 2011, were assigned to a phylogenetic group by PCR. Partial multilocus sequence typing was ...
