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1.
J Vet Intern Med ; 38(3): 1290-1299, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38497217

RESUMEN

Equine herpesvirus-1 (EHV-1) is a highly prevalent and frequently pathogenic infection of equids. The most serious clinical consequences of infection are abortion and equine herpesvirus myeloencephalopathy (EHM). The previous consensus statement was published in 2009 and considered pathogenesis, strain variation, epidemiology, diagnostic testing, vaccination, outbreak prevention and control, and treatment. A recent survey of American College of Veterinary Internal Medicine large animal diplomates identified the need for a revision to this original consensus statement. This updated consensus statement is underpinned by 4 systematic reviews that addressed key questions concerning vaccination, pharmaceutical treatment, pathogenesis, and diagnostic testing. Evidence for successful vaccination against, or effective treatment of EHV-1 infection was limited, and improvements in experimental design and reporting of results are needed in future studies of this important disease. This consensus statement also updates the topics considered previously in 2009.


Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Animales , Caballos , Enfermedades de los Caballos/virología , Enfermedades de los Caballos/prevención & control , Infecciones por Herpesviridae/veterinaria , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/virología , Embarazo , Femenino
2.
J Vet Intern Med ; 2023 Nov 06.
Artículo en Inglés | MEDLINE | ID: mdl-37930113

RESUMEN

BACKGROUND: Equine herpes virus type 1 (EHV-1) infection in horses is associated with respiratory and neurologic disease, abortion, and neonatal death. HYPOTHESIS: Vaccines decrease the occurrence of clinical disease in EHV-1-infected horses. METHODS: A systematic review was performed searching multiple databases to identify relevant studies. Selection criteria were original peer-reviewed research reports that investigated the in vivo use of vaccines for the prevention of disease caused by EHV-1 in domesticated horses. Main outcomes of interest included pyrexia, abortion, neurologic disease, viremia, and nasal shedding. We evaluated risk of bias, conducted exploratory meta-analyses of incidence data for the main outcomes, and performed a GRADE evaluation of the quality of evidence for each vaccine subtype. RESULTS: A total of 1018 unique studies were identified, of which 35 met the inclusion criteria. Experimental studies accounted for 31/35 studies, with the remainder being observational studies. Eight vaccine subclasses were identified including commercial (modified-live, inactivated, mixed) and experimental (modified-live, inactivated, deletion mutant, DNA, recombinant). Risk of bias was generally moderate, often because of underreporting of research methods, and sample sizes were small leading to imprecision in the estimate of the effect size. Several studies reported either no benefit or minimal vaccine efficacy for the primary outcomes of interest. Meta-analyses revealed significant heterogeneity was present, and our confidence in the quality of evidence for most outcomes was low to moderate. CONCLUSIONS AND CLINICAL IMPORTANCE: Our review indicates that commercial and experimental vaccines minimally reduce the incidence of clinical disease associated with EHV-1 infection.

3.
Viruses ; 14(11)2022 11 21.
Artículo en Inglés | MEDLINE | ID: mdl-36423188

RESUMEN

Equid Herpesvirus Myeloencephalopathy (EHM) is a multifactorial disease following an EHV-1 infection in Equidae. We investigated a total of 589 horses on 13 premises in Europe in search of risk factors for the development of EHM. We found that fever (p < 0.001), increasing age (p = 0.032), and female sex (p = 0.042) were risk factors for EHM in a logistic mixed model. Some breeds had a decreased risk to develop EHM compared to others (Shetland and Welsh ponies; p = 0.017; p = 0.031), and fewer EHV-1-vaccinated horses were affected by EHM compared to unvaccinated horses (p = 0.02). Data evaluation was complex due to high variability between outbreaks with regards to construction and environment; viral characteristics and the virus's transmissibility were affected by operational management. This study confirms earlier suspected host-specific risk factors, and our data support the benefit of high vaccine coverage at high-traffic boarding facilities.


Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Caballos , Femenino , Animales , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/veterinaria , Enfermedades de los Caballos/epidemiología , Brotes de Enfermedades/veterinaria , Factores de Riesgo
4.
Vet Clin North Am Equine Pract ; 38(2): 339-362, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-35811201

RESUMEN

Although equine herpesvirus myeloencephalopathy (EHM) is a relatively uncommon manifestation of equine herpesvirus-1 (EHV-1) infection, it can cause devastating losses during outbreaks. Antemortem diagnosis of EHM relies mainly on the molecular detection of EHV-1 in nasal secretions and blood. Management of horses affected by EHM is aimed at supportive nursing and nutritional care, at reducing central nervous system inflammation and preventing thromboembolic sequelae. Horses exhibiting sudden and severe neurologic signs consistent with a diagnosis of EHM pose a definite risk to the surrounding horse population. Consequently, early intervention to prevent the spread of infection is required.


Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Animales , Brotes de Enfermedades/veterinaria , Infecciones por Herpesviridae/veterinaria , Enfermedades de los Caballos/prevención & control , Caballos
5.
Viruses ; 13(11)2021 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-34834949

RESUMEN

(1) Background: Equine arteritis virus (EAV) infection causes reproductive losses and systemic vasculitis in susceptible equidae. The intact male becomes the virus' reservoir upon EAV infection, as it causes a chronic-persistent infection of the accessory sex glands. Infected semen is the main source of virus transmission. (2) Here, we describe acute EAV infection and spread in a stallion population after introduction of new members to the group. (3) Conclusions: acute clinical signs, acute phase detection of antigen via (PCR) nasal swabs or (EDTA) blood, and seroconversion support the idea of transmission via seminal fluids into the respiratory tract(s) of others. This outbreak highlights EAV's horizontal transmission via the respiratory tract. This route should be considered in a chronic-persistently infected herd, when seronegative animals are added to the group.


Asunto(s)
Infecciones por Arterivirus/epidemiología , Infecciones por Arterivirus/veterinaria , Brotes de Enfermedades , Equartevirus , Enfermedades de los Caballos/epidemiología , Animales , Infecciones por Arterivirus/transmisión , Infecciones por Arterivirus/virología , Transmisión de Enfermedad Infecciosa , Enfermedades de los Caballos/virología , Caballos , Masculino , Masturbación , Infección Persistente , Sistema Respiratorio/virología , Semen/virología
6.
Viruses ; 13(9)2021 09 06.
Artículo en Inglés | MEDLINE | ID: mdl-34578356

RESUMEN

A final diagnosis in a horse with clinical signs of encephalopathy can be challenging despite the use of extensive diagnostics. Clinical signs are often not pathognomonic and need to be interpreted in combination with (specific) laboratory results and epidemiological data of the geographical region of the origin of the case(s). Here we describe the diagnostic pathway of tick-borne encephalitis virus infection in two horses using established molecular diagnostic methods and a novel in situ hybridization technique to differentiate between regionally important/emerging diseases for central Europe: (i) hepatoencephalopathy, (ii) Borna disease virus, and (iii) West Nile virus infections.


Asunto(s)
Virus de la Encefalitis Transmitidos por Garrapatas , Encefalitis Transmitida por Garrapatas/diagnóstico , Encefalitis Transmitida por Garrapatas/virología , Enfermedades de los Caballos/diagnóstico , Enfermedades de los Caballos/virología , Animales , Austria , Encéfalo/patología , Encéfalo/virología , Virus de la Encefalitis Transmitidos por Garrapatas/genética , Encefalitis Transmitida por Garrapatas/epidemiología , Encefalitis Transmitida por Garrapatas/patología , Alemania , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/patología , Caballos , Hibridación in Situ , Ixodes/virología , Fiebre del Nilo Occidental/epidemiología , Fiebre del Nilo Occidental/virología , Virus del Nilo Occidental/genética
7.
Viruses ; 13(8)2021 07 22.
Artículo en Inglés | MEDLINE | ID: mdl-34452295

RESUMEN

In May 2018, Wolvega Equine Hospital (WEH) experienced an EHV-1 outbreak. This outbreak caused significant economic losses and negative publicity for the hospital. How should hospitals prepare themselves for these outbreaks and prevent shedding of the virus on multiple neighboring premises? The hospital transformed most of its activities into mobile practice and the entire infected hospital population was moved to a separate remote location. The hospital was cleaned and disinfected according to the latest recommendations before reopening. Four neighboring professional equine businesses and three privately owned premises were affected by the spread of the virus from the hospital population and initiated quarantine restrictions. Equine hospitals should prepare themselves for EHV-1 outbreaks as the intake of the virus cannot be prevented. A management protocol should include public information protocols, swift client information and quarantine measures that ensure quick containment of the outbreak. Timely reopening of the hospital can be achieved by rehousing the contaminated population. It should also include good regulations with clients and a properly carried out release protocol. Equine sports organizations should establish sufficient vaccination coverage in order to decrease the frequency of EHV-1 outbreaks.


Asunto(s)
Infección Hospitalaria/veterinaria , Brotes de Enfermedades/veterinaria , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1 , Enfermedades de los Caballos/epidemiología , Hospitales Veterinarios , Animales , Control de Enfermedades Transmisibles , Infección Hospitalaria/prevención & control , Infección Hospitalaria/terapia , Femenino , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/terapia , Enfermedades de los Caballos/prevención & control , Enfermedades de los Caballos/terapia , Caballos , Masculino , Países Bajos/epidemiología , Cuarentena
8.
Pathogens ; 10(6)2021 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-34198884

RESUMEN

Equid herpesvirus-1 (EHV-1) causes respiratory disease, abortion and myeloencephalopathy in horses worldwide. As member of the Alphaherpesvirinae, latency is key to EHV-1 epidemiology. EHV-1 latent infection has been detected in the trigeminal ganglion (TG), respiratory associated lymphoid tissue (RALT) and peripheral blood mononuclear cells (PBMC) but additional locations are likely. The aim of this study was to investigate the distribution of viral DNA throughout the equine body. Twenty-five horses divided into three groups were experimentally infected via intranasal instillation with one of three EHV-1 viruses and euthanized on Day 70, post infection. During necropsy, TG, various sympathetic/parasympathetic ganglia of head, neck, thorax and abdomen, spinal cord dorsal root ganglia, RALT, mesenteric lymph nodes, spleen and PBMC of each horse were collected. Genomic viral loads and L-(late) gene transcriptional activity in each tissue and PBMC were measured using qPCR. In addition, immunohistochemistry (IHC) was applied on neural parenchyma tissue sections. EHV-1 DNA was detected in many neural and lymphoid tissue sections, but not in PBMC. L-gene transcriptional activity was not detected in any sample, and translational activity was not apparent on IHC. Tissue tropism differed between the Ab4 wild type and the two mutant viruses.

9.
Pathogens ; 10(5)2021 Apr 29.
Artículo en Inglés | MEDLINE | ID: mdl-33947126

RESUMEN

Equid herpesvirus type 1 (EHV-1) causes several outbreaks of abortion and/or equid herpesvirus-associated myeloencephalopathy (EHM) worldwide each year. EHM is of great concern, as permanent neurological gait anomalies can leave a horse unfit for future use. The study assesses the risk factors associated with the occurrence of EHM. During an unmitigated outbreak, 141 adult horses/ponies of several distinct breeds were evaluated-using multiple Bayesian logistic regression calculating the odds ratios for breed, age, and sex. In total, 33 of the 141 horses showed signs of EHM. Fjord horses and warmblood horses were overrepresented among those developing EHM. The pony breeds, Welsh and Shetland ponies, were underrepresented. In addition, age and sex were not associated with the risk for EHM. The main limitation was that it was a retrospective analysis with some flaws of documentation. It can be concluded that breed was a significant risk factor for developing EHM during this outbreak.

10.
J Equine Vet Sci ; 96: 103318, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33349405

RESUMEN

A 5-month-old draft horse filly was presented with incontinence and severe perivulvar dermatitis, which developed during the previous 2 months. Left-sided ectopic ureter entering in the caudal vaginal lumen, signs of cervix hypoplasia, and urine accumulation in the uterus were found during initial vaginal endoscopy. Therefore, a left ureter-nephrectomy was conducted under general anesthesia. Additionally, a cytogenetic examination was performed, which showed a XO monosomy with a 63,X/64,XX mosaic. This is the first case report presenting a chromosome abnormality in a draft horse filly combined with a left-sided ectopic ureter. Cytogenetic evaluation is recommended in any female horse with developmental abnormalities of the cervix, uterus, ovaries, or with irregularities of estrus.


Asunto(s)
Enfermedades de los Caballos , Uréter , Incontinencia Urinaria , Animales , Femenino , Enfermedades de los Caballos/diagnóstico , Caballos , Monosomía/genética , Incontinencia Urinaria/veterinaria , Útero , Cromosoma X
11.
Equine Vet J ; 53(2): 349-355, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32557765

RESUMEN

BACKGROUND: Equid herpesvirus type 1 (EHV-1) is ubiquitous in equine populations causing respiratory disease, and complications including late-term abortion and neurological disease. Eradication of EHV-1 from housing environments that typically contain unsealed wood and porous bedding materials can be challenging. However, consideration should be given to take advantage of the viral envelope's susceptibility to environmental conditions. OBJECTIVE: To determine environmental persistence of EHV-1 on materials and in environmental conditions commonly found in equine facilities. We hypothesised that environmental conditions and materials would limit environmental persistence of EHV-1 in horse housing environments. STUDY DESIGN: Experimental study. METHODS: Standard inoculum of EHV-1 strain OH03 was applied to leather, polyester-cotton fabric, two bedding materials (pinewood shavings and wheat straw) and polystyrene (plastic), and placed under three different environmental conditions (4°C, indoors and outdoors). Virus titration and quantitative PCR (qPCR) were performed at six time points between 0 and 48 hours and the number of plaque-forming units (PFUs) was determined. RESULTS: Viable EHV-1 was recovered up to 48 hours from all material-environmental condition combinations, with persistence decreasing over time. In general, outdoor environment had the greatest impact, irrespective of material tested, followed by indoor environment and 4°C. On average, wood shavings had the greatest impact on persistence, followed by leather, straw, fabric and polystyrene. MAIN LIMITATIONS: The inoculum used in this study was not in a milieu consistent with nasal secretions. As such, virus particles may have been more sensitive to the materials and/or environmental conditions evaluated. CONCLUSIONS: Environmental factors had variable effects on environmental persistence. Although there were significant reductions in PFUs within the first 3 hours, irrespective of environment-material evaluated, viable virus was still recovered at 48 hours likely representing a transmission risk. Barrier precautions should be used to prevent spread of EHV-1 from unrecognised environmental reservoirs.


Asunto(s)
Infecciones por Herpesviridae , Herpesvirus Équido 1 , Enfermedades de los Caballos , Enfermedades Respiratorias , Animales , Femenino , Infecciones por Herpesviridae/prevención & control , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/genética , Enfermedades de los Caballos/prevención & control , Caballos , Embarazo , Reacción en Cadena en Tiempo Real de la Polimerasa/veterinaria , Enfermedades Respiratorias/veterinaria
12.
Front Vet Sci ; 7: 621, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33102556

RESUMEN

Upper respiratory tract infections with Equid Herpesvirus 1 (EHV-1) typically result in a peripheral blood mononuclear cell-associated viremia, which can lead to vasculopathy in the central nervous system. Primary EHV-1 infection also likely establishes latency in trigeminal ganglia (TG) via retrograde axonal transport and in respiratory tract-associated lymphatic tissue. However, latency establishment and reactivation are poorly understood. To characterize the pathogenesis of EHV-1 latency establishment and maintenance, two separate groups of yearling horses were experimentally infected intranasally with EHV-1, strain Ab4, and euthanized 30 days post infection (dpi), (n = 9) and 70 dpi (n = 6). During necropsy, TG, sympathetic trunk (ST), retropharyngeal and mesenteric lymph nodes (RLn, MesLn) and kidney samples were collected. Viral DNA was detected by quantitative PCR (qPCR) in TG, ST, RLn, and MesLn samples in horses 30 and 70 dpi. The number of positive TG, RLn and MesLn samples was reduced when comparing horses 30 and 70 dpi and the viral copy number in TG and RLn significantly declined from 30 to 70 dpi. EHV-1 late gene glycoprotein B reverse transcriptase PCR and IHC results for viral protein were consistently negative, thus lytic replication was excluded in the present study. Mild inflammation could be detected in all neural tissue samples and inflammatory infiltrates mainly consisted of CD3+ T-lymphocytes (T-cells), frequently localized in close proximity to neuronal cell bodies. To identify latently infected cell types, in situ hybridization (ISH, RNAScope®) detecting viral DNA was used on selected qPCR- positive neural tissue sections. In ganglia 30 dpi, EHV-1 ISH signal was located in the neurons of TG and ST, but also in non-neuronal support or interstitial cells surrounding the neuron. In contrast, distinct EHV-1 signal could only be observed in neurons of TG 70 dpi. Overall, detection of latent EHV-1 in abdominal tissue samples and non-neuronal cell localization suggests, that EHV-1 uses T-cells during viremia as alternative route toward latency locations in addition to retrograde neuronal transport. We therefore hypothesize that EHV-1 follows the same latency pathways as its close relative human pathogen Varicella Zoster Virus.

13.
Front Neuroanat ; 14: 614929, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33390909

RESUMEN

Introduction of new imaging modalities for the equine brain have refocused attention on the horse as a natural model for ethological, neuroanatomical, and neuroscientific investigations. As opposed to imaging studies, strategies for equine neurodissection still lack a structured approach, standardization and reproducibility. In contrast to other species, where adapted protocols for sampling have been published, no comparable guideline is currently available for equids. Hence, we developed a species-specific slice protocol for whole brain vs. hemispheric dissection and tested its applicability and practicability in the field, as well as its neuroanatomical accuracy and reproducibility. Dissection steps are concisely described and depicted by schematic illustrations, photographs and instructional videos. Care was taken to show the brain in relation to the raters' hands, cutting devices and bench surface. Guidance is based on a minimum of external anatomical landmarks followed by geometric instructions that led to procurement of 14 targeted slabs. The protocol was performed on 55 formalin-fixed brains by three groups of investigators with different neuroanatomical skills. Validation of brain dissection outcomes addressed the aptitude of slabs for neuroanatomical studies as opposed to simplified routine diagnostic purposes. Across all raters, as much as 95.2% of slabs were appropriate for neuroanatomical studies, and 100% of slabs qualified for a routine diagnostic setting. Neither autolysis nor subfixation significantly affected neuroanatomical accuracy score, while a significant negative effect was observed with brain extraction artifacts. Procedure times ranged from 14 to 66 min and reached a mean duration of 23.25 ± 7.93 min in the last of five trials in inexperienced raters vs. 16 ± 2.83 min in experts, while acceleration of the dissection did not negatively impact neuroanatomical accuracy. This protocol, derived analogously to the consensus report of the International Veterinary Epilepsy Task Force in dogs and cats, allows for systematic, quick and easy dissection of the equine brain, even for inexperienced investigators. Obtained slabs feature virtually all functional subcompartments at suitable planes for both diagnostic and neuroscientific investigations and complement the data obtained from imaging studies. The instructive protocol and brain dissection videos are available in Supplementary Material.

14.
Immun Inflamm Dis ; 7(3): 130-149, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31141308

RESUMEN

INTRODUCTION: Equine asthma represents a naturally occurring animal model for human allergic neutrophilic asthma. Inhalative nanoparticle-bound cytosine-phosphate-guanosine (CpG-GNP) immunotherapy, independent of specific allergens, has already shown promising clinical and immunological results in previous studies and offers the possibility to treat the underlying cause of the disease. This study analyses the relationship between dose and response, and evaluates a possible long-term effect. METHODS: In the prospective, randomised, double-blind clinical field study, 29 horses suffering from equine asthma received 10 inhalation treatments with either 187.5 µg CpG-GNP (CpG single dose [CpGsd]; n = 11), 375 µg CpG-GNP double dose (CpG double dose [CpGdd]; n = 9) (q48h for 20 days) or 1600 µg beclomethasone (n = 9) (q24h for 10 days). Each horse was examined three times: before the treatment (I), immediately after the 10 inhalations (II), and 8 weeks after the final inhalation (III). The three groups were compared according to clinical and laboratory parameters. The study examined the sustainability of the long-term effect of the treatment after 8 weeks, as well as the tolerability of the formula as a double dose. RESULTS: The CpGsd resulted in a significant improvement in 82% of the parameters, the CpGdd in 72%. In the long-term evaluation, the CpGsd showed a significant improvement in 100% of the parameters in comparison to the initial values, the CpGdd in 67%. On the immunological level, the bronchoalveolar lavage revealed a significant reduction of IL-4, IL-8, and interferon-γ. CONCLUSION: Both CpG groups displayed significant improvements in clinical and laboratory parameters, especially regarding the long-term effect of CpGsd. Doubling the CpG dose did not result in any improvement in comparison to the original single dose. On the immunological level, an anti-inflammatory, as well as an immunomodulatory effect, apart from a Th2-dominated immune response, could be observed. This immunomodulatory inhalation treatment could indicate a new possibility for human allergic asthma therapy.


Asunto(s)
Asma , Fosfatos de Dinucleósidos , Modelos Animales de Enfermedad , Enfermedades de los Caballos , Inmunomodulación , Oligodesoxirribonucleótidos , Animales , Administración por Inhalación , Asma/inmunología , Asma/terapia , Asma/veterinaria , Líquido del Lavado Bronquioalveolar/química , Líquido del Lavado Bronquioalveolar/inmunología , Citocinas/inmunología , Citocinas/metabolismo , Fosfatos de Dinucleósidos/administración & dosificación , Fosfatos de Dinucleósidos/inmunología , Fosfatos de Dinucleósidos/uso terapéutico , Relación Dosis-Respuesta a Droga , Método Doble Ciego , Enfermedades de los Caballos/inmunología , Enfermedades de los Caballos/terapia , Caballos , Inmunomodulación/inmunología , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Oligodesoxirribonucleótidos/uso terapéutico , Estudios Prospectivos , Resultado del Tratamiento
15.
Front Vet Sci ; 6: 59, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30886853

RESUMEN

Histopathological differences in horses infected with equine herpesvirus type 1 (EHV-1) of differing neuropathogenic potential [wild-type (Ab4), polymerase mutant (Ab4 N752), EHV-1/4 gD mutant (Ab4 gD4)] were evaluated to examine the impact of viral factors on clinical disease, tissue tropism and pathology. Three of 8 Ab4 infected horses developed Equine Herpesvirus Myeloencephalopathy (EHM) requiring euthanasia of 2 horses on day 9 post-infection. None of the other horses showed neurologic signs and all remaining animals were sacrificed 10 weeks post-infection. EHM horses had lymphohistiocytic vasculitis and lymphocytic infiltrates in the lungs, spinal cord, endometrium and eyes. EHV-1 antigen was detected within the eyes and spinal cord. In 3/6 of the remaining Ab4 infected horses, 4/9 Ab4 N752 infected horses, and 8/8 Ab4 gD4 infected horses, choroiditis was observed. All males had interstitial lymphoplasmacytic and/or histiocytic orchitis and EHV-1 antigen was detected. In conclusion, only animals sacrificed due to EHM developed overt vasculitis in the CNS and the eye. Mild choroiditis persisted in many animals and appeared to be more common in Ab4 gD4 infected animals. Finally, we report infiltrates and changes in the reproductive organs of all males associated with EHV-1 antigen. While the exact significance of these changes is unclear, these findings raise concern for long-term effects on reproduction and prolonged shedding of virus through semen.

16.
J Gen Virol ; 98(6): 1439-1454, 2017 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-28631601

RESUMEN

Despite the importance of neurological disorders associated with herpesviruses, the mechanism by which these viruses influence the central nervous system (CNS) has not been definitively established. Owing to the limitations of studying neuropathogenicity of human herpesviruses in their natural host, many aspects of their pathogenicity and immune response are studied in animal models. Here, we present an important model system that enables studying neuropathogenicity of herpesviruses in the natural host. Equine herpesvirus type 1 (EHV-1) is an alphaherpesvirus that causes a devastating neurological disease (EHV-1 myeloencephalopathy; EHM) in horses. Like other alphaherpesviruses, our understanding of virus neuropathogenicity in the natural host beyond the essential role of viraemia is limited. In particular, information on the role of different viral proteins for virus transfer to the spinal cord endothelium in vivo is lacking. In this study, the contribution of two viral proteins, DNA polymerase (ORF30) and glycoprotein D (gD), to the pathogenicity of EHM was addressed. Furthermore, different cellular immune markers, including alpha-interferon (IFN-α), gamma-interferon (IFN-γ), interleukin-10 (IL-10) and interleukin-1 beta (IL-1ß), were identified to play a role during the course of the disease.


Asunto(s)
Biomarcadores/análisis , Encefalitis Viral/patología , Infecciones por Herpesviridae/complicaciones , Infecciones por Herpesviridae/virología , Herpesvirus Équido 1/patogenicidad , Interacciones Huésped-Patógeno , Proteínas Virales/metabolismo , Animales , Femenino , Infecciones por Herpesviridae/patología , Caballos , Masculino , Modelos Animales , Factores de Virulencia/metabolismo
17.
Vet Microbiol ; 170(1-2): 28-38, 2014 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-24560592

RESUMEN

Equine herpesvirus-1 (EHV-1) is the cause of respiratory disease, abortion and myelitis in horses worldwide. Protection following infection or vaccination is typically incomplete and this lack of protective immunity is thought to be due to the immunomodulatory properties of EHV-1. EHV-1 immune modulation is likely initiated early in the infection cycle at the respiratory epithelium, but to date, immunity to EHV-1 at the epithelial cell barrier remains poorly characterized. Thus, the purpose of this study was to use a recently established primary equine respiratory epithelial cell culture (EREC) system to characterize innate immunity to EHV-1. Differentiated ERECs were inoculated with a neuropathogenic strain of EHV-1 and cytokine responses were determined using quantitative real-time polymerase chain reaction and ELISA. Major histocompatibility complex (MHC)-I and MHC-II as well as toll-like receptor (TLR)3 and TLR9 protein expression were examined using fluorescence activated cell-sorting analysis and chemotaxis of neutrophils and monocytes were evaluated using chemotaxis assays. Infection with EHV-1 resulted in increased expression of TLR3 and 9 as well as inflammatory cytokines (IL-1, TNF-alpha, IFN-alpha, and IL-6) and chemokines (IL-8, MCP-1). In contrast, EHV-1 infection caused marked decreases of MHC-I and MHC-II expression as well as a reduction in IFN-gamma production. In summary, these results provide an initial characterization of the early immune response to EHV-1 at the epithelial cell barrier and show that, while EHV-1 maintains induction of an inflammatory response, it causes an attenuation of IFN-gamma responses and down-modulates expression of MHC-I and MHC-II, which are important molecules for antigen presentation.


Asunto(s)
Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/inmunología , Enfermedades de los Caballos/inmunología , Interacciones Huésped-Patógeno/inmunología , Inmunidad Innata/inmunología , Mucosa Respiratoria/inmunología , Mucosa Respiratoria/virología , Animales , Células Cultivadas , Quimiocinas/genética , Quimiocinas/inmunología , Citocinas/genética , Citocinas/inmunología , Células Epiteliales/inmunología , Células Epiteliales/virología , Regulación de la Expresión Génica/inmunología , Infecciones por Herpesviridae/inmunología , Caballos , Internalización del Virus
18.
Vet Res ; 44: 118, 2013 Dec 05.
Artículo en Inglés | MEDLINE | ID: mdl-24308772

RESUMEN

Equine herpesvirus myeloencephalitis (EHM) remains one of the most devastating manifestations of equine herpesvirus type 1 (EHV-1) infection but our understanding of its pathogenesis remains rudimentary, partly because of a lack of adequate experimental models. EHV-1 infection of the ocular vasculature may offer an alternative model as EHV-1-induced chorioretinopathy appears to occur in a significant number of horses, and the pathogenesis of EHM and ocular EHV-1 may be similar. To investigate the potential of ocular EHV-1 as a model for EHM, and to determine the frequency of ocular EHV-1, our goal was to study: (1) Dissemination of virus following acute infection, (2) Development and frequency of ocular lesions following infection, and (3) Utility of a GFP-expressing virus for localization of the virus in vivo. Viral antigen could be detected following acute infection in ocular tissues and the central nervous system (experiment 1). Furthermore, EHV-1 infection resulted in multifocal choroidal lesions in 90% (experiment 2) and 50% (experiment 3) of experimentally infected horses, however ocular lesions did not appear in vivo until between 3 weeks and 3 months post-infection. Taken together, the timing of the appearance of lesions and their ophthalmoscopic features suggest that their pathogenesis may involve ischemic injury to the chorioretina following viremic delivery of virus to the eye, mirroring the vascular events that result in EHM. In summary, we show that the frequency of ocular EHV-1 is 50-90% following experimental infection making this model attractive for testing future vaccines or therapeutics in an immunologically relevant age group.


Asunto(s)
Coriorretinitis/veterinaria , Encefalomielitis/veterinaria , Angiografía con Fluoresceína/métodos , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/aislamiento & purificación , Animales , Coriorretinitis/epidemiología , Coriorretinitis/patología , Coriorretinitis/virología , Encefalomielitis/epidemiología , Encefalomielitis/patología , Encefalomielitis/virología , Angiografía con Fluoresceína/veterinaria , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Infecciones por Herpesviridae/epidemiología , Infecciones por Herpesviridae/patología , Infecciones por Herpesviridae/virología , Enfermedades de los Caballos/epidemiología , Enfermedades de los Caballos/patología , Enfermedades de los Caballos/virología , Caballos , Pruebas de Neutralización/veterinaria , Nariz/virología , Distribución Aleatoria , Viremia/veterinaria , Viremia/virología , Esparcimiento de Virus
19.
Vaccine ; 30(46): 6564-72, 2012 Oct 12.
Artículo en Inglés | MEDLINE | ID: mdl-22944628

RESUMEN

Equine herpesvirus-1 (EHV-1) continues to cause both sporadic and epidemic abortions despite extensive vaccination. Lack of progress in the development of protective vaccines may be hindered by the lack of equine abortion models that employ contemporary EHV-1 strains. The objective of our experiments was to compare a contemporary EHV-1 strain with a previously described challenge strain, and to quantify EHV-1 loads in various maternal and fetal tissues. Infection experiments were performed in two groups of 7 pregnant pony mares at 270-290 days of gestation with a contemporary EHV-1 strain (University of Findlay 2003 isolate - OH03) or an EHV-1 strain isolated over 30 years ago, and previously described in abortion models (Ab4). All mares in both groups exhibited nasal viral shedding and viremia. Infection with OH03 resulted in 1/7 abortion and infection with Ab4 resulted in 5/7 abortions. In the OH03 challenge, placentas of foals delivered at term showed little detectable virus, while the aborted fetus expressed high levels of virus infection in the spleen and liver, lower levels in the lung and thymus, and lowest levels in the chorioallantois. After Ab4 challenge, high viral loads were detected in fetal and placental tissues in abortions. In the two normal deliveries, the chorioallantois contained virus levels comparable with the chorioallantois of aborted foals and both foals shed EHV-1 starting on day 4 of life, but were clinically healthy. Our results demonstrate the continued importance of strain selection for abortion models, and this study is the first report of viral load quantification using contemporary methods. Extremely high EHV-1 loads in decidua from abortions illustrate the infection risk posed to other horses.


Asunto(s)
Aborto Espontáneo/virología , Aborto Veterinario/virología , Feto/virología , Infecciones por Herpesviridae/veterinaria , Herpesvirus Équido 1/aislamiento & purificación , Placenta/virología , Carga Viral , Estructuras Animales/virología , Animales , Femenino , Infecciones por Herpesviridae/virología , Herpesvirus Équido 1/patogenicidad , Caballos , Mucosa Nasal/virología , Embarazo , Viremia/virología , Esparcimiento de Virus
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