Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.
Abstract: Equine herpesvirus type 1 (EHV-1) is a main cause of respiratory disease, abortion, and encephalomyelopathy in horses. Monocytic cells (CD172a(+)) are the main carrier cells of EHV-1 during primary infection and are proposed to serve as a "Trojan horse" to facilitate the dissemination of EHV-1 to target organs. However, the mechanism by which EHV-1 is transferred from CD172a(+) cells to endothelial cells (EC) remains unclear. The aim of this study was to investigate EHV-1 transmission between these two cell types. We hypothesized that EHV-1 employs specific strategies to promote the adhesion of infected CD172a(+) cells to EC to facilitate EHV-1 spread. Here, we demonstrated that EHV-1 infection of CD172a(+) cells resulted in a 3- to 5-fold increase in adhesion to EC. Antibody blocking experiments indicated that α4β1, αLβ2, and αVβ3 integrins mediated adhesion of infected CD172a(+) cells to EC. We showed that integrin-mediated phosphatidylinositol 3-kinase (PI3K) and ERK/MAPK signaling pathways were involved in EHV-1-induced CD172a(+) cell adhesion at early times of infection. EHV-1 replication was enhanced in adherent CD172a(+) cells, which correlates with the production of tumor necrosis factor alpha (TNF-α). In the presence of neutralizing antibodies, approximately 20% of infected CD172a(+) cells transferred cytoplasmic material to uninfected EC and 0.01% of infected CD172a(+) cells transmitted infectious virus to neighboring cells. Our results demonstrated that EHV-1 infection induces adhesion of CD172a(+) cells to EC, which enhances viral replication, but that transfer of viral material from CD172a(+) cells to EC is a very specific and rare event. These findings give new insights into the complex pathogenesis of EHV-1. Objective: Equine herpesvirus type 1 (EHV-1) is a highly prevalent pathogen worldwide, causing frequent outbreaks of abortion and myeloencephalopathy, even in vaccinated horses. After primary replication in the respiratory tract, EHV-1 disseminates via cell-associated viremia in peripheral blood mononuclear cells (PBMC) and subsequently infects the endothelial cells (EC) of the pregnant uterus or central nervous system, leading in some cases to abortion and/or neurological disorders. Recently, we demonstrated that CD172a(+) monocytic carrier cells serve as a "Trojan horse" to facilitate EHV-1 spread from blood to target organs. Here, we investigated the mechanism underlying the transmission of EHV-1 from CD172a(+) cells to EC. We demonstrated that EHV-1 infection induces cellular changes in CD172a(+) cells, promoting their adhesion to EC. We found that both cell-to-cell contacts and the secretion of soluble factors by EC activate EHV-1 replication in CD172a(+) cells. This facilitates transfer of cytoplasmic viral material to EC, resulting mainly in a nonproductive infection. Our findings give new insights into how EHV-1 may spread to EC of target organs in vaccinated horses.
Copyright © 2015, American Society for Microbiology. All Rights Reserved.
Publication Date: 2015-08-19 PubMed ID: 26292328PubMed Central: PMC4621108DOI: 10.1128/JVI.01589-15Google Scholar: Lookup
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- Journal Article
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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 explores how the Equine Herpesvirus Type 1 (EHV-1), a cause of respiratory disease, abortion, and encephalomyelopathy in horses, uses CD172a+ monocytic cells to spread to endothelial cells, thereby propagating the infection.
Study Objective and Hypothesis
- The main objective of the research was to understand the process by which EHV-1 migrates from CD172a+ cells to endothelial cells (EC).
- To fulfil this objective, the researchers hypothesized that the virus employs methods to promote the adhesion of the infected CD172a+ cells to the EC in order to disseminate the virus further.
Methodology and Findings
- The research showed that the infection of CD172a+ cells by EHV-1 resulted in the infected cells adhering to the EC 3 to 5 times more.
- The study also identified specific antibodies, α4β1, αLβ2, and αVβ3 integrins, that caused adhesion of the infected CD172a+ cells to EC.
- Through in-depth investigation, it was established that phosphatidylinositol 3-kinase (PI3K) and ERK/MAPK signaling pathways were involved in this virus-induced cell adhesion at the early stages of infection.
- The study discovered that EHV-1 replication was enhanced in CD172a+ cells that adhered to EC, and this corresponded with the production of the tumor necrosis factor alpha (TNF-α).
- The researchers also found that around 20% of the infected CD172a+ cells shared cytoplasmic material with uninfected EC, and 0.01% infected cells transmitted the virus to neighboring cells.
Conclusion
- The study concluded that EHV-1 infection leads to an increased adhesion of CD172a+ cells to EC, which in turn enhances viral replication.
- However, the transfer of infected material from CD172a+ cells to EC is a rare and specific event.
- The findings suggest a complex pathogenesis of EHV-1 and offer new insights into how this virus spreads to EC in vaccinated horses.
Cite This Article
APA
Laval K, Favoreel HW, Poelaert KC, Van Cleemput J, Nauwynck HJ.
(2015).
Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.
J Virol, 89(21), 10912-10923.
https://doi.org/10.1128/JVI.01589-15 Publication
Researcher Affiliations
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium.
- Department of Virology, Parasitology and Immunology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium hans.nauwynck@ugent.be.
MeSH Terms
- Analysis of Variance
- Animals
- Belgium
- Blotting, Western
- Cell Adhesion / physiology
- Endothelial Cells / virology
- Enzyme-Linked Immunosorbent Assay
- Flow Cytometry
- Herpesviridae Infections / physiopathology
- Herpesviridae Infections / veterinary
- Herpesvirus 1, Equid / physiology
- Horse Diseases / physiopathology
- Horse Diseases / virology
- Horses
- Monocytes / metabolism
- Monocytes / virology
- Signal Transduction / physiology
- Virus Internalization
- Virus Replication / physiology
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