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Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a+ Monocytic Cells upon Adhesion to Endothelial Cells.
- Source :
-
Journal of virology [J Virol] 2015 Nov; Vol. 89 (21), pp. 10912-23. Date of Electronic Publication: 2015 Aug 19. - Publication Year :
- 2015
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Abstract
- Unlabelled: 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.<br />Importance: 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.<br /> (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)
- Subjects :
- Analysis of Variance
Animals
Belgium
Blotting, Western
Cell Adhesion physiology
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
Herpesviridae Infections physiopathology
Horses
Monocytes metabolism
Signal Transduction physiology
Virus Internalization
Endothelial Cells virology
Herpesviridae Infections veterinary
Herpesvirus 1, Equid physiology
Horse Diseases physiopathology
Horse Diseases virology
Monocytes virology
Virus Replication physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1098-5514
- Volume :
- 89
- Issue :
- 21
- Database :
- MEDLINE
- Journal :
- Journal of virology
- Publication Type :
- Academic Journal
- Accession number :
- 26292328
- Full Text :
- https://doi.org/10.1128/JVI.01589-15