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Viruses2021; 13(3); 356; doi: 10.3390/v13030356

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

Abstract: 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.
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Publication Date: 2021-02-24 PubMed ID: 33668216PubMed Central: PMC7995974DOI: 10.3390/v13030356Google Scholar: Lookup
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  • Journal Article
  • Research Support
  • Non-U.S. Gov't

Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on studying the host factors that are associated with equine herpesvirus myeloencephalopathy (EHM), a condition affecting horses globally, by analyzing the transcriptome of Peripheral blood mononuclear cells (PBMCs) from horses.

Research Purpose and Methodology

  • Equine herpesvirus-1 is identified as a cause for EHM, respiratory disease, and abortion in horses across the world. Up to 14% of infected horses are affected by EHM, with the prevalence increasing to 70% in aged horses. It is suspected that an age-related weakening immune system contributes to the EHM development, but concrete information about the host factors involved is limited.
  • The researchers utilized the “old mare model” to study EHM. The study was designed to simulate EHM via EHV-1 infection in aged horses and to subsequently observe and analyze PBMCs – both pre-infection and during viremia – the presence of viruses in the horse’s blood.
  • RNA sequencing was employed to examine any changes in gene expression, providing a comparative view of the transcriptome of horses that developed clinical EHM and those that did not. A set of horses that developed EHM is referred to as the EHM group, and those which did not develop EHM as the non-EHM group.

Findings and Observations

  • The study found that horses affected by EHM didn’t display any signs of respiratory disease. On the contrary, non-EHM horses exhibited significant respiratory issues from the 2nd day after infection.
  • Several immune pathways behaved differently in EHM horses when compared to non-EHM horses while responding to EHV-1. Prominent changes were noticed in the IL-6 gene expression, AP-1 mediated T-cell activation, and a visible skew towards a T-helper 2 phenotype.
  • Besides, the research discovered a dysregulation in the coagulation pathway and an upregulated response to progesterone in EHM horses.

Conclusion

  • Overall, this research sheds light on the possible host factors playing a critical role in the development of EHM in horses. This deepens our understanding of EHM pathogenesis and paves the way for more targeted treatments or preventative strategies in the future.

Cite This Article

APA
Zarski LM, Giessler KS, Jacob SI, Weber PSD, McCauley AG, Lee Y, Soboll Hussey G. (2021). Identification of Host Factors Associated with the Development of Equine Herpesvirus Myeloencephalopathy by Transcriptomic Analysis of Peripheral Blood Mononuclear Cells from Horses. Viruses, 13(3), 356. https://doi.org/10.3390/v13030356

Publication

Viruses
ISSN: 1999-4915
NlmUniqueID: 101509722
Country: Switzerland
Language: English
Volume: 13
Issue: 3
PII: 356

Researcher Affiliations

Zarski, Lila M
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Giessler, Kim S
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Jacob, Sarah I
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Weber, Patty Sue D
  • Department of Large Animal Clinical Sciences, Michigan State University, East Lansing, MI 48824, USA.
McCauley, Allison G
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Lee, Yao
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.
Soboll Hussey, Gisela
  • Department of Pathobiology and Diagnostic Investigation, Michigan State University, East Lansing, MI 48824, USA.

MeSH Terms

  • Animals
  • Female
  • Gene Expression / genetics
  • Gene Expression / immunology
  • Gene Expression Profiling / methods
  • Herpesviridae Infections / immunology
  • Herpesviridae Infections / virology
  • Herpesvirus 1, Equid / immunology
  • Horse Diseases / immunology
  • Horse Diseases / virology
  • Horses
  • Interleukin-6 / genetics
  • Interleukin-6 / immunology
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / virology
  • Lymphocyte Activation / genetics
  • Lymphocyte Activation / immunology
  • Male
  • Respiratory Tract Diseases / genetics
  • Respiratory Tract Diseases / immunology
  • Respiratory Tract Diseases / virology
  • T-Lymphocytes / immunology
  • T-Lymphocytes / virology
  • T-Lymphocytes, Helper-Inducer / immunology
  • T-Lymphocytes, Helper-Inducer / virology
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Up-Regulation / genetics
  • Up-Regulation / immunology

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collec-tion, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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