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Frontiers in veterinary science2018; 5; 34; doi: 10.3389/fvets.2018.00034

Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In Vitro.

Abstract: Equine herpesvirus type 1 (EHV-1) is a ubiquitous and highly contagious pathogen that causes a range of disease severities with outbreaks of notable economic impact. Given the limitations in immune protection of current vaccines and the limited effectiveness of antiviral drugs on EHV-1 infections , improved treatment measures are needed to control disease. The use of drugs that alter the epigenetic state of herpes simplex virus genome has been shown to limit viral primary infection and reactivation both and . Therefore, we tested the hypothesis that maintaining a repressive epigenetic state on the EHV-1 genome in the host equine cell would decrease viral load during lytic infection. Equine fetal kidney cells (EFKCs) or isolated peripheral blood leukocytes were treated with (a) the nucleoside analog ganciclovir; (b) the histone demethylase inhibitor OG-L002; (c) both ganciclovir and OG-L002; or (d) dimethyl sulfoxide (DMSO, vehicle control); and then infected with a clinical EHV-1 isolate. Treatment of EFKCs with ganciclovir (mean 22.3 DNA copies per cell,  = 0.0005), OG-L002 (mean 25.6,  = 0.005) or both ganciclovir and OG-L002 (mean 7.1,  = 0.0001) resulted in decreased EHV-1 viral load at 24 h post-infection (hpi) in comparison with DMSO (mean 42.0), with greater impact using the combined treatment. Further, EHV-1 gene expression at 3 hpi decreased when EFKCs were infected in the presence of ganciclovir ( = 0.04) and combined treatment of ganciclovir and OG-L002 ( = 0.0003). In contrast, under similar conditions, neither ganciclovir nor OG-L002 suppressed EHV-1 infection in leukocytes. Differences between cell types, drug penetrance, or drug turnover, may have contributed to the distinct effects observed in this study.
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Publication Date: 2018-03-12 PubMed ID: 29594155PubMed Central: PMC5857540DOI: 10.3389/fvets.2018.00034Google Scholar: Lookup
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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 investigates the impact of a histone demethylase inhibitor and a nucleoside analog drug on the activity and infection rates of Equine herpesvirus type 1 (EHV-1) in equine cells. Findings from the study suggest that combined treatment using both drugs resulted in a decreased viral load and gene expression in equine fetal kidney cells (EFKCs), but not in leukocytes.

About EHV-1 And Why This Research Is Needed

  • Equine herpesvirus type 1 (EHV-1) is a widespread and extremely contagious virus that can cause various diseases in horses, representing significant economic implications.
  • The effectiveness of current vaccines and antiviral drugs are limited, stressing the need for improved treatment measures to control the disease.
  • Drugs that manipulate the epigenetic state of the herpes simplex virus genome have shown promise in restraining viral infection. Therefore, the researchers hypothesised that similar methods might work on EHV-1 and help in reducing viral load during infection.

Research Methodology

  • Equine Fetal Kidney Cells (EFKCs) or isolated peripheral blood leukocytes, a type of white blood cell, were treated with the nucleoside analog ganciclovir, the histone demethylase inhibitor OG-L002, both drugs combined, or a vehicle control (DMSO).
  • The treated cells were then infected with a clinically isolated strain of EHV-1.

Findings and Conclusions

  • At 24 hours post-infection, the three treatment options all resulted in decreased viral loads when compared to the vehicle control, with the combined treatment producing the most substantial impact.
  • The expression of EHV-1 genes was reduced when the EKFCs were infected in the presence of ganciclovir or the combined treatment at 3 hours post-infection.
  • Notably, no suppression of EHV-1 infection was observed in leukocytes when treated under similar conditions.
  • The researchers suggest that differences between cellular types, drug penetration, or drug turnover could have contributed to the distinct effects observed between EKFCs and leukocytes.
  • In conclusion, while the findings are promising for EFKCs, further investigations are needed to understand why leukocytes didn’t respond similarly and to explore the full potential of these treatment options.

Cite This Article

APA
Tallmadge RL, Žygelytė E, Van de Walle GR, Kristie TM, Felippe MJB. (2018). Effect of a Histone Demethylase Inhibitor on Equine Herpesvirus-1 Activity In Vitro. Front Vet Sci, 5, 34. https://doi.org/10.3389/fvets.2018.00034

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 5
Pages: 34
PII: 34

Researcher Affiliations

Tallmadge, Rebecca L
  • Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Žygelytė, Emilija
  • Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Van de Walle, Gerlinde R
  • Baker Institute for Animal Health, Cornell University, Ithaca, NY, United States.
Kristie, Thomas M
  • Molecular Genetics Section, Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MA, United States.
Felippe, M Julia B
  • Equine Immunology Laboratory, Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

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