Equine Herpesviruses

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Viral Pathogens".

Deadline for manuscript submissions: closed (10 September 2021) | Viewed by 24855

Special Issue Editor


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Guest Editor
Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, 784 Wilson Rd, East Lansing, MI 48824, USA
Interests: veterinary virology; herpesviruses; immunology
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Special Issue Information

Dear Colleagues,

The most relevant equine herpesviruses (EHV) in horses include EHV-1, EHV-2, EHV-3, EHV-4 and EHV-5. These viruses fall into two main subfamilies: the alphaherpesvirinae (EHV-1, EHV-3 and EHV-4), and the gammaherpesvirinae (EHV-2 and EHV-5) and are ubiquitous in horses. Clinical manifestations in horses include respiratory disease, ocular disease, genital lesions, abortions, neonatal foal death and neurological disease.

Currently most research is focused on EHV-1, because secondary disease manifestations like abortions and neurological disease are unique to EHV-1 and have significant economic impact. However, much can be learned from identifying similarities and differences of all the equine herpesviruses. The scope of this special issue will be to further our understanding of the unique viral features and virus-host interactions of equine herpesviruses. We invite authors to submit original research or review articles investigating equine herpesviruses with a focus on the following:

  • Viral genetics
  • Disease and disease models
  • Diagnosis
  • Pathogenesis
  • Viral and host risk factors
  • Innate and adaptive immunity and immune evasion
  • Treatment and prevention
  • Latency establishment and reactivation

Dr. Gisela Soboll Hussey
Guest Editor

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Keywords

  • equine herpesvirus
  • equine herpesvirus encephalomyelopathy
  • equine coital exanthema virus
  • equine multinodular pulmonary fibrosis
  • genomic structure
  • pathogenesis
  • immunity
  • vaccination
  • latency

Published Papers (8 papers)

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Research

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14 pages, 943 KiB  
Article
Equid herpesvirus-1 Distribution in Equine Lymphoid and Neural Tissues 70 Days Post Infection
by Susanna Samoilowa, Kim S. Giessler, Carlos E. Medina Torres, Gisela Soboll Hussey, Allison Allum, Robert Fux, Christin Jerke, Matti Kiupel, Kaspar Matiasek, Dodd G. Sledge and Lutz S. Goehring
Pathogens 2021, 10(6), 707; https://doi.org/10.3390/pathogens10060707 - 05 Jun 2021
Cited by 2 | Viewed by 2409
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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10 pages, 624 KiB  
Article
Apparent Breed Predilection for Equid Herpesvirus-1-Associated Myeloencephalopathy (EHM) in a Multiple-Breed Herd
by Eva Klouth, Yury Zablotski and Lutz S. Goehring
Pathogens 2021, 10(5), 537; https://doi.org/10.3390/pathogens10050537 - 29 Apr 2021
Cited by 5 | Viewed by 1765
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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15 pages, 1845 KiB  
Article
Interferon Gamma Inhibits Equine Herpesvirus 1 Replication in a Cell Line-Dependent Manner
by Seong K. Kim, Akhalesh K. Shakya and Dennis J. O’Callaghan
Pathogens 2021, 10(4), 484; https://doi.org/10.3390/pathogens10040484 - 16 Apr 2021
Cited by 3 | Viewed by 1953
Abstract
The sole equine herpesvirus 1 (EHV-1) immediate-early protein (IEP) is essential for viral replication by transactivating viral immediate-early (IE), early (E), and late (L) genes. Here, we report that treatment of mouse MH-S, equine NBL6, and human MRC-5 cells with 20 ng/mL of [...] Read more.
The sole equine herpesvirus 1 (EHV-1) immediate-early protein (IEP) is essential for viral replication by transactivating viral immediate-early (IE), early (E), and late (L) genes. Here, we report that treatment of mouse MH-S, equine NBL6, and human MRC-5 cells with 20 ng/mL of IFN-γ reduced EHV-1 yield by 1122-, 631-, and 10,000-fold, respectively. However, IFN-γ reduced virus yield by only 2–4-fold in mouse MLE12, mouse L-M, and human MeWo cells compared to those of untreated cells. In luciferase assays with the promoter of the EHV-1 early regulatory EICP0 gene, IFN-γ abrogated trans-activation activity of the IEP by 96% in MH-S cells, but only by 21% in L-M cells. Similar results were obtained in assays with the early regulatory UL5 and IR4 promoter reporter plasmids. IFN-γ treatment reduced IEP protein expression by greater than 99% in MH-S cells, but only by 43% in L-M cells. The expression of IEP and UL5P suppressed by IFN-γ was restored by JAK inhibitor treatment, indicating that the inhibition of EHV-1 replication is mediated by JAK/STAT1 signaling. These results suggest that IFN-γ blocks EHV-1 replication by inhibiting the production of the IEP in a cell line-dependent manner. Affymetrix microarray analyses of IFN-γ-treated MH-S and L-M cells revealed that five antiviral ISGs (MX1, SAMHD1, IFIT2, NAMPT, TREX1, and DDX60) were upregulated 3.2–18.1-fold only in MH-S cells. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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14 pages, 2208 KiB  
Article
Evaluation of the Variability of the ORF34, ORF68, and MLST Genes in EHV-1 from South Korea
by Hyung-Woo Kang, Eun-Yong Lee, Kyoung-Ki Lee, Mi-Kyeong Ko, Ji-Young Park, Yeon-Hee Kim, Kyunghyun Lee, Eun-Jin Choi, Jongho Kim, ByungJae So, Choi-Kyu Park and Hye-Young Jeoung
Pathogens 2021, 10(4), 425; https://doi.org/10.3390/pathogens10040425 - 02 Apr 2021
Cited by 2 | Viewed by 1538
Abstract
Equine herpesvirus-1 (EHV-1) is an important pathogen in horses. It affects horses worldwide and causes substantial economic losses. In this study, for the first time, we characterized EHV-1 isolates from South Korea at the molecular level. We then aimed to determine the genetic [...] Read more.
Equine herpesvirus-1 (EHV-1) is an important pathogen in horses. It affects horses worldwide and causes substantial economic losses. In this study, for the first time, we characterized EHV-1 isolates from South Korea at the molecular level. We then aimed to determine the genetic divergences of these isolates by comparing them to sequences in databases. In total, 338 horse samples were collected, and 12 EHV-1 were isolated. We performed ORF30, ORF33, ORF68, and ORF34 genetic analysis and carried out multi-locus sequence typing (MLST) of 12 isolated EHV-1. All isolated viruses were confirmed as non-neuropathogenic type, showing N752 of ORF30 and highly conserved ORF33 (99.7–100%). Isolates were unclassified using ORF68 analysis because of a 118 bp deletion in nucleotide sequence 701–818. Seven EHV-1 isolates (16Q4, 19R166-1, 19R166-6, 19/10/15-2, 19/10/15-4, 19/10/18-2, 19/10/22-1) belonged to group 1, clade 10, based on ORF34 and MLST analysis. The remaining 5 EHV-1 isolates (15Q25-1, 15D59, 16Q5, 16Q40, 18D99) belonged to group 7, clade 6, based on ORF34 and MLST analysis. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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30 pages, 3835 KiB  
Article
Transcriptomic Profiling of Equine and Viral Genes in Peripheral Blood Mononuclear Cells in Horses during Equine Herpesvirus 1 Infection
by Lila M. Zarski, Patty Sue D. Weber, Yao Lee and Gisela Soboll Hussey
Pathogens 2021, 10(1), 43; https://doi.org/10.3390/pathogens10010043 - 07 Jan 2021
Cited by 6 | Viewed by 3518
Abstract
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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Review

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10 pages, 963 KiB  
Review
Equine Coital Exanthema: New Insights on the Knowledge and Leading Perspectives for Treatment and Prevention
by María Aldana Vissani, Armando Mario Damiani and María Edith Barrandeguy
Pathogens 2021, 10(8), 1055; https://doi.org/10.3390/pathogens10081055 - 20 Aug 2021
Cited by 2 | Viewed by 4220
Abstract
Equine coital exanthema (ECE) is a highly contagious, venereally-transmitted mucocutaneous disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genital organs of mares and stallions, and caused by equid alphaherpesvirus 3 (EHV-3). The infection is endemic worldwide and [...] Read more.
Equine coital exanthema (ECE) is a highly contagious, venereally-transmitted mucocutaneous disease, characterized by the formation of papules, vesicles, pustules and ulcers on the external genital organs of mares and stallions, and caused by equid alphaherpesvirus 3 (EHV-3). The infection is endemic worldwide and the virus is transmitted mainly through direct contact during sexual intercourse and by contaminated instruments during reproductive maneuvers in breeding facilities. The disease does not result in systemic illness, infertility or abortion, yet it does have a negative impact on the equine industry as it forces the temporary withdrawal of affected animals with the consequent disruption of mating activities in breeding facilities. The purpose of this review is to provide up-to-date relevant information on the knowledge of EHV-3 infection and to analyze new approaches on diagnostics, treatment and prevention in the interest of minimizing the negative consequences of ECE in light of the current situation of the equine industry. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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10 pages, 2756 KiB  
Review
Environmental Detection and Potential Transmission of Equine Herpesviruses
by Anisha Dayaram, Peter A. Seeber and Alex D. Greenwood
Pathogens 2021, 10(4), 423; https://doi.org/10.3390/pathogens10040423 - 01 Apr 2021
Cited by 13 | Viewed by 4406
Abstract
Equine herpesviruses (EHV) are a major health concern for domestic and wild equids and represent one of the most economically important disease agents of horses. Most known EHVs are transmitted directly between individuals as a result of direct exposure to exudates and aerosols. [...] Read more.
Equine herpesviruses (EHV) are a major health concern for domestic and wild equids and represent one of the most economically important disease agents of horses. Most known EHVs are transmitted directly between individuals as a result of direct exposure to exudates and aerosols. However, accumulating evidence suggests that environmental transmission may play a role including air, water, and fomites. Here, we reviewed studies on environmental stability and transmission of EHVs, which may influence viral dynamics and the use of environmental samples for monitoring EHV shedding. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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Other

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9 pages, 520 KiB  
Case Report
Investigation of an EHV-1 Outbreak in the United States Caused by a New H752 Genotype
by Nicola Pusterla, Samantha Barnum, Julia Miller, Sarah Varnell, Barbara Dallap-Schaer, Helen Aceto and Aliza Simeone
Pathogens 2021, 10(6), 747; https://doi.org/10.3390/pathogens10060747 - 13 Jun 2021
Cited by 24 | Viewed by 3602
Abstract
Here we report on an EHV-1 outbreak investigation caused by a novel genotype H752 (histidine in amino acid position 752 of the ORF 30 gene). The outbreak involved 31 performance horses. Horses were monitored over a period of 35 days for clinical [...] Read more.
Here we report on an EHV-1 outbreak investigation caused by a novel genotype H752 (histidine in amino acid position 752 of the ORF 30 gene). The outbreak involved 31 performance horses. Horses were monitored over a period of 35 days for clinical signs, therapeutic outcome and qPCR results of EHV-1 in blood and nasal secretions. The morbidity of the EHV-1 outbreak was 84% with 26 clinically infected horses displaying fever and less frequently anorexia and distal limb edema. Four horses showed mild transient neurological deficits. Clinically diseased horses experienced high viral load of EHV-1 in blood and/or nasal secretions via qPCR, while subclinically infected horses had detectable EHV-1 mainly in nasal secretions. The majority of infected horses showed a rise in antibody titers to EHV-1 during the outbreak. All 31 horses were treated with valacyclovir, while clinically infected horses further received flunixin meglumine and sodium heparin. This investigation highlights various relevant aspects of an EHV-1 outbreak caused by a new H752 genotype: (i) importance of early detection of EHV-1 infection; (ii) diagnostic challenge to assess H752 genotype; (iii) apparent benefit of valacyclovir use in the early stage of the outbreak; and (iv) weekly testing of blood and nasal secretions by qPCR in order to monitor individual infection status and lift quarantine. Full article
(This article belongs to the Special Issue Equine Herpesviruses)
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