Equine Herpesvirus Myeloencephalopathy Research Articles

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses.

Herpesviruses establish a well-adapted balance with their host's immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1β, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-β (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this 'at-risk' immunophenotype.

Long-term performance of show-jumping horses and relationship with severity of ataxia and complications associated with myeloencephalopathy caused by equine herpes virus-1.

Equine herpesvirus myeloencephalopathy (EHM) has severe impact on the sport horse population. Study the influence of EHM on the likelihood of affected horses to return to their previous performance and investigate the association of clinical variables with prognosis. Twenty-six horses positive for equine herpesvirus type 1 (EHV-1) were admitted to a veterinary teaching hospital (VTH) during a natural EHM outbreak at an international jumping event. Data collected from the VTH, the International Equestrian Federation, and surveys completed by the riders and horse owners were retrospectively analyzed. Horses affected by EHM had 68% chance of returning to exercise, and 52.9% were able to achieve their preoutbreak performance level. Horses with an ataxia grade at admission ≥4/5 had an increased fatality rate (P < .05) and 10% chance of reaching their preoutbreak performance level. None of the horses with both vascular and urinary complications returned to their previous performance level. Finally, horses vaccinated against EHV-1 and those with urinary complications had a 71.4% and 43.7% fatality rate, respectively. Horses affected by EHM were able to return to their previous performance levels, but certain clinical variables were negatively associated with postoutbreak performance. Ataxia grade upon admission and the development of systemic signs of vasculitis and urinary complications were potential poor prognostic indicators in sport horses. Variables linked to fatality included prior vaccination against EHV-1, ataxia grade upon admission, and the development of urinary complications.

Updated ACVIM consensus statement on equine herpesvirus-1.

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.

Detection of equine herpesvirus-1 (EHV-1) in urine samples during outbreaks of equine herpesvirus myeloencephalopathy.

Real-time PCR is the diagnostic technique of choice for the diagnosis and control of equine herpesvirus-1 (EHV-1) in an outbreak setting. The presence of EHV-1 in nasal swabs (NS), whole blood, brain and spinal cord samples has been extensively described; however, there are no reports on the excretion of EHV-1 in urine, its DNA detection patterns, and the role of urine in viral spread during an outbreak. To determine the presence of EHV-1 DNA in urine during natural infection and to compare the DNA detection patterns of EHV-1 in urine, buffy coat (BC) and NS. Descriptive study of natural infection. Urine and whole blood/NS samples were collected at different time points during the hospitalisation of 21 horses involved in two EHV-1 myeloencephalopathy outbreaks in 2021 and 2023 in Spain. Quantitative real-time PCR was performed to compare the viral DNA load between BC-urine samples in 2021 and NS-urine samples in 2023. Sex, age, breed, presence of neurological signs, EHV-1 vaccination status and treatment data were recorded for all horses. A total of 18 hospitalised horses during the 2021 and 2023 outbreaks were positive for EHV-1, and viral DNA was detected in urine samples from a total of 11 horses in both outbreaks. Compared with BC samples, DNA presence was detected in urine samples for longer duration and with slightly higher concentration; however, compared with NS, detection of EHV-1 in urine was similar in duration with lower DNA concentrations. Limited sample size, different sampling times and protocols (BC vs. NS) in two natural infection outbreak settings. EHV-1 was detected in the urine from naturally infected horses. Urine should be considered as complimentary to blood and NS in diagnosis of EHV-1 infection.

Effects of individualised rehabilitation for horses with equine herpesvirus myeloencephalopathy

SummaryIn 2019, a Swedish outbreak of equine herpes virus type 1 (EHV‐1) led to varying neurological symptoms also known as EHM (equine herpes myeloencephalopathy). Nineteen of the 39 exposed horses developed EHM. EHM outbreaks have become more common in recent decades and can result in large economic losses for the horse industry in addition to clear welfare implications. However, there is limited information about the estimated time to recovery from EHM and return to previous level of performance and there is limited published information regarding neurological rehabilitation in horses. Our objective was to describe and evaluate the potential benefit of implementing individual rehabilitation plans for horses recovering from EHM. Four horses with EHV‐1 and with clinical signs of neurological dysfunction were selected. All horses were initially hospitalised at an intensive care unit between 4 and 9 days and approximately 3 months after the outbreak they were considered sufficiently recovered to start a rehabilitation programme. The programs mainly focused on regaining proprioception, core stability and strength with consideration given to fatigue in the horse and risk to the handlers. A repeated neurological examination was performed six times over the first year and the rehabilitation programs were modified accordingly. The owners considered the horses ‘normal’, both mentally and physically, between 6 and 8 months after the outbreak. All horses were back to their previous level of performance after 8–11 months. A limitation of the study was a small study population with no control group. Our conclusions are that horses suffering from severe EHM may return to an acceptable athletic function given time and an individually adapted rehabilitation program. To potentially show that an individually adapted rehabilitation plan brings the horse back to acceptable function faster than nonspecific rehabilitation, a case‐control study would be required.

Anti-inflammatory compounds reduce equine herpesvirus type 1 replication and cell-to-cell spread.

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 and effective therapeutic interventions can be developed and delivered. In this study, we examined the ability of four non-steroidal anti-inflammatory drugs (NSAIDs), a steroidal anti-inflammatory drug (dexamethasone), a Rho-kinase (ROCK) inhibitor, and a JAK/STAT inhibitor (AG490) to reduce EHV-1 virus yields and cell-to-cell spread. We show that the NSAID, flunixin meglumine (FM), and the JAK/STAT inhibitor, AG490, significantly reduced virus yields in endothelial and epithelial cell lines, and this inhibition was similar for two neurologic and two non-neurologic EHV-1 strains. In addition to reducing virus yields, AG490 and FM also significantly reduced the ability of EHV-1 to spread laterally from cell to cell.

Investigation of the Systemic Antibody Response and Antigen Detection Following Intranasal Administration of Two Commercial Equine Herpesvirus-1 Vaccines to Adult Horses.

EHV-1 vaccines are often administered intranasally during emergency situation such as outbreaks of equine herpesvirus myeloencephalopathy. However, there is currently no data available on the efficacy of such protocols, nor the diagnostic challenge when recently vaccinated horses become clinically infected and nasal secretions are collected to support a diagnosis of EHV-1 infection. Therefore, the objective of this study was to determine if two commercially available EHV-1 vaccines, a killed-adjuvanted (Calvenza) and a modified-live (Rhinomune) EHV-1 vaccine, could induce a measurable systemic antibody response postintranasal administration. A second objective was to determine the detection time of EHV-1 in nasal secretions by qPCR following the intranasal administration of the respective EHV-1 vaccines. Thirty healthy adult horses, with no recent EHV-1 vaccine administration, were randomly assigned to one of three groups: Rhinomune group, Calvenza group, and unvaccinated control group. Total Ig and isotype-specific IgG4/7 against EHV-1 measured pre- and 30-days post-vaccination were not different amongst the three study groups. Vaccine-derived EHV-1 was only detected in the two EHV-1 vaccine groups with 9/10 horses in the Rhinomune group and 8/10 horses in the Calvenza group testing qPCR-positive for EHV-1 for 1 to 3 days. There was no significant difference in number of horses testing qPCR-positive for EHV-1 and absolute quantitation of EHV-1 in nasal secretions by qPCR between the two vaccine groups. The intranasal administration of two commercial EHV-1 vaccines did not elicit a systemic immune response. Further, vaccine derived EHV-1 could be detected in the majority of the intranasally vaccinated horses, potentially impacting diagnostic interpretation of EHV-1 during outbreak situations.

How do we prevent and control future outbreaks of equine herpesvirus myeloencephalopathy at equestrian gatherings?

How do we prevent and control future outbreaks of equine herpesvirus myeloencephalopathy at equestrian gatherings?

Clinical insights: Equine herpesvirus myeloencephalopathy: The conundrum of vaccination in performance and leisure horses

Clinical insights: Equine herpesvirus myeloencephalopathy: The conundrum of vaccination in performance and leisure horses

Temporal variability between detection of fever and positive PCR from nasal and blood samples in a 2016 outbreak of equine herpesvirus myeloencephalopathy in California

Temporal variability between detection of fever and positive PCR from nasal and blood samples in a 2016 outbreak of equine herpesvirus myeloencephalopathy in California

A Live-Attenuated Equine Influenza Vaccine Stimulates Innate Immunity in Equine Respiratory Epithelial Cell Cultures That Could Provide Protection From Equine Herpesvirus 1.

Equine herpesvirus 1 (EHV-1) ubiquitously infects horses worldwide and causes respiratory disease, abortion, and equine herpesvirus myeloencephalopathy. Protection against EHV-1 disease is elusive due to establishment of latency and immune-modulatory features of the virus. These include the modulation of interferons, cytokines, chemokines, antigen presentation, and cellular immunity. Because the modulation of immunity likely occurs at the site of first infection—the respiratory epithelium, we hypothesized that the mucosal influenza vaccine Flu Avert® I.N. (Flu Avert), which is known to stimulate strong antiviral responses, will enhance antiviral innate immunity, and that these responses would also provide protection from EHV-1 infection. To test our hypothesis, primary equine respiratory epithelial cells (ERECs) were treated with Flu Avert, and innate immunity was evaluated for 10 days following treatment. The timing of Flu Avert treatment was also evaluated for optimal effectiveness to reduce EHV-1 replication by modulating early immune responses to EHV-1. The induction of interferons, cytokine and chemokine mRNA expression, and protein secretion was evaluated by high-throughput qPCR and multiplex protein analysis. Intracellular and extracellular EHV-1 titers were determined by qPCR. Flu Avert treatment resulted in the modulation of IL-8, CCL2, and CXCL9 starting at days 5 and 6 post-treatment. Coinciding with the timing of optimal chemokine induction, our data also suggested the same timing for reduction of EHV-1 replication. In combination, our results suggest that Flu Avert may be effective at counteracting some of the immune-modulatory properties of EHV-1 at the airway epithelium and the peak for this response occurs 5–8 days post-Flu Avert treatment. Future in vivo studies are needed to investigate Flu Avert as a prophylactic in situations where EHV-1 exposure may occur.

Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses.

Equine herpesvirus-1 is the cause of respiratory disease, abortion, and equine herpesvirus myeloencephalopathy (EHM) in horses worldwide. EHM affects as many as 14% of infected horses and a cell-associated viremia is thought to be central for EHM pathogenesis. While EHM is infrequent in younger horses, up to 70% of aged horses develop EHM. The aging immune system likely contributes to EHM pathogenesis; however, little is known about the host factors associated with clinical EHM. Here, we used the “old mare model” to induce EHM following EHV-1 infection. Peripheral blood mononuclear cells (PBMCs) of horses prior to infection and during viremia were collected and RNA sequencing with differential gene expression was used to compare the transcriptome of horses that did (EHM group) and did not (non-EHM group) develop clinical EHM. Interestingly, horses exhibiting EHM did not show respiratory disease, while non-EHM horses showed significant respiratory disease starting on day 2 post infection. Multiple immune pathways differed in EHM horses in response to EHV-1. These included an upregulation of IL-6 gene expression, a dysregulation of T-cell activation through AP-1 and responses skewed towards a T-helper 2 phenotype. Further, a dysregulation of coagulation and an upregulation of elements in the progesterone response were observed in EHM horses.

Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection.

Equine herpesvirus 1 (EHV-1) affects horses worldwide and causes respiratory disease, abortions, and equine herpesvirus myeloencephalopathy (EHM). Following infection, a cell-associated viremia is established in the peripheral blood mononuclear cells (PBMCs). This viremia is essential for transport of EHV-1 to secondary infection sites where subsequent immunopathology results in diseases such as abortion or EHM. Because of the central role of PBMCs in EHV-1 pathogenesis, our goal was to establish a gene expression analysis of host and equine herpesvirus genes during EHV-1 viremia using RNA sequencing. When comparing transcriptomes of PBMCs during peak viremia to those prior to EHV-1 infection, we found 51 differentially expressed equine genes (48 upregulated and 3 downregulated). After gene ontology analysis, processes such as the interferon defense response, response to chemokines, the complement protein activation cascade, cell adhesion, and coagulation were overrepresented during viremia. Additionally, transcripts for EHV-1, EHV-2, and EHV-5 were identified in pre- and post-EHV-1-infection samples. Looking at micro RNAs (miRNAs), 278 known equine miRNAs and 855 potentially novel equine miRNAs were identified in addition to 57 and 41 potentially novel miRNAs that mapped to the EHV-2 and EHV-5 genomes, respectively. Of those, 1 EHV-5 and 4 equine miRNAs were differentially expressed in PBMCs during viremia. In conclusion, this work expands our current knowledge about the role of PBMCs during EHV-1 viremia and will inform the focus on future experiments to identify host and viral factors that contribute to clinical EHM.

Genome-wide association study for host genetic factors associated with equine herpesvirus type-1 induced myeloencephalopathy.

BackgroundEquid herpesvirus (EHV‐1) infections in horses can lead to equine herpesvirus myeloencephalopathy (EHM), characterised by neurological clinical signs. The sporadic occurrence of the disease in horse herds suggests a host genetic component. A recent study reported an association between the occurrence of EHM and genetic markers on horse chromosome 6 (ECA6).ObjectivesTo investigate the association of EHM with genetic host factors, especially with reference to the association reported for ECA6.Study designGenome‐wide association study (GWAS) was conducted based on 94 horses that had EHV‐1 infections and comparing the 27 developing clinical EHM to the 67 which did not.MethodsDNA samples were tested from 94 horses for 382,529 single nucleotide polymorphisms (SNPs) with the Affymetrix Axiom 670K SNP array to identify possible associations with EHM. The data analysis included tests for basic, additive, dominant and recessive modes of inheritance, haplotype associations and runs of homozygosity (ROH).ResultsResults from this study did not identify significant SNPs, haplotypes or ROH associations with the development of EHM following EHV‐1 infections and excluded the involvement of a recessive genetic factor in the susceptibility to develop EHM.Main limitationsSample size and complex phenotype.ConclusionsThe results exclude the involvement of a recessive genetic factor in the susceptibility to develop clinically apparent EHM but do not have the power to exclude the involvement of other, complex host genetic factors. Furthermore, there was no association between development of EHM and genes on equine chromosome 6, as previously reported.

Equine herpesvirus-1 genotype did not significantly affect clinical signs and disease outcome in 65 horses diagnosed with equine herpesvirus-1 myeloencephalopathy

The objective of this study was to determine if the genotype of equine herpesvirus-1 (EHV-1) impacted clinical disease and outcome of horses with laboratory confirmed equine herpesvirus myeloencephalopathy (EHM). Medical records from 65 horses diagnosed with EHM from 2011 to 2019 were reviewed for signalment, presence and severity of clinical signs (lethargy, fever, ataxia, urinary incontinence) and outcome. Horses were further grouped based on the EHV-1 genotype into neuropathic (D752) or non-neuropathic (N752) EHV-1 infection. Between the two EHV-1 genotype groups, age and sex distributions were similar, although breed distribution was different (Quarter Horses and Saddlebreds were overrepresented and Warmbloods were underrepresented in the EHV-1 D752 group compared to the EHV-1 N752 group; P = 0.009). Lethargy, fever, ataxia and outcome were not significantly different between the two EHV-1 genotype groups (P > 0.05). However, urinary incontinence was significantly more frequently reported in horses infected with the D752 genotype of EHV-1 (P=0.04). Contrary to previous studies, the present study showed no difference in frequency of genotype (D752 or N752) among 65 horses with EHM and, with the exception of urinary incontinence, no difference in clinical disease or outcome related to the EHV-1 genotype.

An Equine Herpesvirus Type 1 (EHV-1) Ab4 Open Reading Frame 2 Deletion Mutant Provides Immunity and Protection from EHV-1 Infection and Disease.

Equine herpesvirus type 1 (EHV-1) outbreaks continue to occur despite widely used vaccination. Therefore, development of EHV-1 vaccines providing improved immunity and protection is ongoing. Here, an open reading frame 2 deletion mutant of the neuropathogenic EHV-1 strain Ab4 (Ab4ΔORF2) was tested as a vaccine candidate. Three groups of horses (n = 8 each) were infected intranasally with Ab4ΔORF2 or the parent Ab4 virus or were kept as noninfected controls. Horses infected with Ab4ΔORF2 had reduced fever and nasal virus shedding compared to those infected with Ab4 but mounted similar adaptive immunity dominated by antibody responses. Nine months after the initial infection, all horses were challenged intranasally with Ab4. Previously noninfected horses (control/Ab4) displayed clinical signs, shed large amounts of virus, and developed cell-associated viremia. In contrast, 5/8 or 3/8 horses previously infected with Ab4ΔORF2 or Ab4, respectively, were fully protected from challenge infection as indicated by the absence of fever, clinical disease, nasal virus shedding, and viremia. All of these outcomes were significantly reduced in the remaining, partially protected 3/8 (Ab4ΔORF2/Ab4) and 5/8 (Ab4/Ab4) horses. Protected horses had EHV-1-specific IgG4/7 antibodies prior to challenge infection, and intranasal antibodies increased rapidly postchallenge. Intranasal inflammatory markers were not detectable in protected horses but quickly increased in control/Ab4 horses during the first week after infection. Overall, our data suggest that preexisting nasal IgG4/7 antibodies neutralize EHV-1, prevent viral entry, and thereby protect from disease, viral shedding, and cell-associated viremia. In conclusion, improved protection from challenge infection emphasizes further evaluation of Ab4ΔORF2 as a vaccine candidate.IMPORTANCE Nasal equine herpesvirus type 1 (EHV-1) shedding is essential for virus transmission during outbreaks. Cell-associated viremia is a prerequisite for the most severe disease outcomes, abortion and equine herpesvirus myeloencephalopathy (EHM). Thus, protection from viremia is considered essential for preventing EHM. Ab4ΔORF2 vaccination prevented EHV-1 challenge virus replication in the upper respiratory tract in fully protected horses. Consequently, these neither shed virus nor developed cell-associated viremia. Protection from virus shedding and viremia during challenge infection in combination with reduced virulence at the time of vaccination emphasizes ORF2 deletion as a promising modification for generating an improved EHV-1 vaccine. During this challenge infection, full protection was linked to preexisting local and systemic EHV-1-specific antibodies combined with rapidly increasing intranasal IgG4/7 antibodies and lack of nasal type I interferon and chemokine induction. These host immune parameters may constitute markers of protection against EHV-1 and be utilized as indicators for improved vaccine development and informed vaccination strategies.

Histopathologic Findings Following Experimental Equine Herpesvirus 1 Infection of Horses

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.

Molecular characterisation of equid alphaherpesvirus 1 strains isolated from aborted fetuses in Poland

BackgroundEquid alphaherpesvirus 1 (EHV-1) is one of the main infectious causative agents of abortion in mares and can also be associated with stillbirth, neonatal foal death, rhinopneumonitis in young horses and a neurological disorder called equine herpesvirus myeloencephalopathy (EHM). The neuropathogenicity of the virus was shown to be significantly higher in EHV-1 strains that carry a single nucleotide point (SNP) mutation in the ORF30, which encodes a catalytic subunit of viral DNA polymerase (ORF30 D752). Another gene, ORF68 is frequently used for phylogenetic analysis of EHV-1.Methods27 EHV-1 strains isolated from aborted equine fetuses in Poland, collected between 1993 and 2017, were subjected to PCR targeting the open reading frames (ORFs) 30 and 68 of the EHV-1 genome. PCR products obtained were sequenced and SNPs were analyzed and compared to sequences available in GenBank.ResultsNone of the analyzed sequences belonged to the ORF30 D752neuropathogenic genotype: all EHV-1 belonged to the non-neuropathogenic variant N752. On the basis of ORF68 sequences, the majority of EHV-1 sequences (76.9%) cannot be assigned to any of the known groups; only six sequences (23.1%) clustered within groups II and IV.ConclusionsEHV-1 strains obtained from abortion cases belong to the non-neuropathogenic genotype. Many EHV-1 ORF68 sequences have similar SNPs to those already described in Poland, but a clear geographical distribution was not observed. A single particular ORF68 sequence type was observed in strains isolated from 2001 onwards.

Asinine herpesvirus-3 (equine herpesvirus-8)-associated neurological disease in a donkey

A 30-year-old female donkey with pituitary pars intermedia dysfunction (PPID) was referred to the Department of Equine Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, for losing weight despite good...

Efficacy of the early administration of valacyclovir hydrochloride for the treatment of neuropathogenic equine herpesvirus type-1 infection in horses.

OBJECTIVE To determine whether prophylactic administration of valacyclovir hydrochloride versus initiation of treatment at the onset of fever would differentially protect horses from viral replication and clinical disease attributable to equine herpesvirus type-1 (EHV-1) infection. ANIMALS 18 aged mares. PROCEDURES Horses were randomly assigned to receive an oral placebo (control), treatment at detection of fever, or prophylactic treatment (initiated 1 day prior to viral challenge) and then inoculated intranasally with a neuropathogenic strain of EHV-1. Placebo or valacyclovir was administered orally for 7 or 14 days after EHV-1 inoculation or detection of fever (3 horses/group). Effects of treatment on viral replication and clinical disease were evaluated. Plasma acyclovir concentrations and viremia were assessed to determine inhibitory concentrations of valacyclovir. RESULTS Valacyclovir administration decreased shedding of virus and viremia, compared with findings for control horses. Rectal temperatures and clinical disease scores in horses that received valacyclovir prophylactically for 2 weeks were lower than those in control horses. The severity of but not the risk for ataxia was decreased by valacyclovir administration. Viremia was decreased when steady-state trough plasma acyclovir concentrations were > 0.8 μg/mL, supporting the time-dependent activity of acyclovir. CONCLUSIONS AND CLINICAL RELEVANCE Valacyclovir treatment significantly decreased viral replication and signs of disease in EHV-1-infected horses; effects were greatest when treatment was initiated before viral inoculation, but treatment was also effective when initiated as late as 2 days after inoculation. During an outbreak of equine herpesvirus myeloencephalopathy, antiviral treatment may be initiated in horses at various stages of infection, including horses that have not yet developed signs of viral disease.