Unravelling the first key steps in equine herpesvirus type 5 (EHV5) pathogenesis using ex vivo and in vitro equine models.
Abstract: Equine herpesvirus type 5 (EHV5) is a ubiquitous, yet obscure pathogen in the horse population and is commonly associated with fatal equine multinodular pulmonary fibrosis (EMPF). To date, little is known about the precise pathogenesis of EHV5. Here, we evaluated the dynamics of EHV5 infection in representative ex vivo and in vitro equine models, using immunofluorescence staining and virus titration. EHV5 was unable to infect epithelial cells lining the mucosa of nasal and tracheal explants. Similarly, primary equine respiratory epithelial cells (EREC) were not susceptible to EHV5 following inoculation at the apical or basolateral surfaces. Upon direct delivery of EHV5 particles to lung explants, few EHV5-positive cell clusters were observed at 72 hours post-inoculation (hpi). These EHV5-positive cells were identified as cytokeratin-positive alveolar cells. Next, we examined the potential of EHV5 to infect three distinct equine PBMC populations (CD172a monocytes, CD3 T lymphocytes and Ig light chain B lymphocytes). Monocytes did not support EHV5 replication. In contrast, up to 10% of inoculated equine T and B lymphocytes synthetized intracellular viral antigens 24 hpi and 72 hpi, respectively. Still, the production of mature virus particles was hampered, as we did not observe an increase in extracellular virus titer. After reaching a peak, the percentage of infected T and B lymphocytes decayed, which was partly due to the onset of apoptosis, but not necrosis. Based on these findings, we propose a model for EHV5 pathogenesis in the horse. Uncovering EHV5 pathogenesis is the corner step to finally contain or even eradicate the virus.
Publication Date: 2019-02-18 PubMed ID: 30777128PubMed Central: PMC6380010DOI: 10.1186/s13567-019-0630-6Google Scholar: Lookup
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- Journal Article
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.
This research was carried out to study the progression and mechanism of equine herpesvirus type 5 (EHV5) in horses, a virus associated with fatal respiratory disease. The study utilized both ex vivo (outside the living body) and in vitro (in a laboratory environment) models of the equine respiratory system for this purpose.
Experimentation and Results
- The research first involved analysing the ability of EHV5 to infect different parts of the equine respiratory system. Through the use of immunofluorescence staining and virus titration, it was found that EHV5 could not infect the epithelial cells lining the nasal and tracheal mucosa.
- Similar results were observed for primary equine respiratory epithelial cells, which remained unaffected even after selective inoculation of the virus at their apical or basolateral surfaces.
- Upon direct introduction of EHV5 particles to lung tissue, some infection was observed in alveolar cells, indicating that these cells are a potential target for EHV5.
Effects on Equine PBMC Populations
- The research then moved on to analyse the effect of EHV5 on various types of equine PBMCs (Peripheral Blood Mononuclear Cells), including CD172a monocytes, CD3 T lymphocytes and Ig light chain B lymphocytes.
- Through this analysis, it was found that monocytes did not support EHV5 replication, whereas T and B lymphocytes did, to an extent. Around 10% of these cells synthesized intracellular viral antigens, but the production of mature virus particles was inhibited.
- The number of infected T and B lymphocytes decreased over time, partly because of the initiation of apoptosis (programmed cell death), suggesting that an immune response could be occurring.
Conclusion
- Based on these results, the researchers proposed a model for the pathogenesis of EHV5 in horses.
- This study provides a stepping stone towards understanding the disease caused by EHV5, and may eventually help in developing methods to contain or even eradicate the virus.
Cite This Article
APA
Van Cleemput J, Poelaert KCK, Laval K, Nauwynck HJ.
(2019).
Unravelling the first key steps in equine herpesvirus type 5 (EHV5) pathogenesis using ex vivo and in vitro equine models.
Vet Res, 50(1), 13.
https://doi.org/10.1186/s13567-019-0630-6 Publication
Researcher Affiliations
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium.
- Department of Molecular Biology, Princeton University, 119 Lewis Thomas Laboratory, Washington Road, Princeton, NJ, 08544, USA.
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820, Merelbeke, Belgium. hans.nauwynck@ugent.be.
MeSH Terms
- Animals
- Cell Line
- Epithelial Cells
- Fluorescent Antibody Technique / veterinary
- Gammaherpesvirinae / physiology
- Herpesviridae Infections / veterinary
- Herpesviridae Infections / virology
- Horse Diseases / virology
- Horses
- In Vitro Techniques
- Tumor Virus Infections / veterinary
- Tumor Virus Infections / virology
- Viral Load / veterinary
Grant Funding
- 11Y5415N / Fonds Wetenschappelijk Onderzoek
- 141627 / Agentschap voor Innovatie door Wetenschap en Technologie
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