Equine Herpesvirus Type 1 (EHV‐1) Myeloencephalopathy: a Case Report

Stierstorfer, Birgit; Eichhorn, Werner; Schmahl, W.; Brandmüller, Christine; Kaaden, Oskar‐Rüger; Neubauer, Antonie

doi:10.1046/j.1439-0450.2002.00537.x

Cited by 29 publications

(20 citation statements)

References 26 publications

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“…EHV-1 infection of endothelial cells also induced extravasation of mononuclear cells, resulting in perivascular cuffing and local hemorrhage (50). Based on this, we believe that the adhesion and transfer of EHV-1 from CD172a ϩ monocytic cells to endothelial cells may contribute to clinical thrombosis in horses with EHV-1 infection.…”

Section: Discussionmentioning

confidence: 80%

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a ⁺ Monocytic Cells upon Adhesion to Endothelial Cells

Laval

Favoreel

Poelaert

et al. 2015

J Virol

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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 ␣ 4 ␤ 1 , ␣ L ␤ 2 , and ␣ V ␤ 3 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-␣). 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. IMPORTANCEEquine 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. E quine herpesvirus type 1 (EHV-1), a member of the subfamily Alphaherpesvirinae, is a ubiquitous pathogen in horses, causing...

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Section: Discussionmentioning

confidence: 80%

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a ⁺ Monocytic Cells upon Adhesion to Endothelial Cells

Laval

Favoreel

Poelaert

et al. 2015

J Virol

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“…The virus disseminates via a cell-associated viraemia in PBMCs to target organs such as the pregnant uterus or central nervous system. Here, the virus initiates a secondary replication that may lead in some cases to severe symptoms such as abortion and/or neurological disorders (Edington et al, 1991;Smith et al, 1996;Stierstorfer et al, 2002). Current vaccines do not provide full protection, as EHV-1 can cause a viraemia in the presence of virus-specific antibodies and CTL precursors (O'Neill et al, 1999;Kydd et al, 2006).…”

Section: Introductionmentioning

confidence: 99%

Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases

Laval

Favoreel

Nauwynck

2015

Journal of General Virology

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Equine herpesvirus type 1 (EHV-1) replicates in the epithelial cells of the upper respiratory tract and disseminates through the body via a cell-associated viraemia in monocytic cells, despite the presence of neutralizing antibodies. However, the mechanism by which EHV-1 hijacks immune cells and uses them as 'Trojan horses' in order to disseminate inside its host is still unclear. Here, we hypothesize that EHV-1 delays its replication in monocytic cells in order to avoid recognition by the immune system. We compared replication kinetics in vitro of EHV-1 in RK-13, a cell line fully susceptible to EHV-1 infection, and primary horse cells from the myeloid lineage (CD172a + ). We found that EHV-1 replication was restricted to 4 % of CD172a+ cells compared with 100 % in RK-13 cells. In

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“…Abortion can involve only one or two mares in a herd but also abortion storms can occur on a premise, associated with great economic losses (Allen and Bryans, 1986). Neurological disorders have been reported with increasing frequency (McMartan et al, 1995;Friday et al, 2000;van Maanen et al, 2001;Stierstorfer et al, 2002;van der Meulen et al, 2003a) and during an outbreak many cases may occur with devastating effects.…”

Section: Introductionmentioning

confidence: 99%

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Garré

Meulen

Nugent

et al. 2007

Veterinary Microbiology

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Equine herpesvirus 1 (EHV-1) is an important equine pathogen that causes respiratory disease, abortion, neonatal death and paralysis. Although vaccines are available, they are not fully protective and outbreaks of disease may occur in vaccinated herds. Therefore, there is an urgent need for effective antiviral treatment. For three abortigenic (94P247, 97P70 and 99P96) and three neuropathogenic isolates (97P82, 99P136 and 03P37), the effect of acyclovir, ganciclovir, cidofovir, adefovir, 9-(2-phosphonylmethoxyethyl)-2,6-diaminopurine (PMEDAP) and foscarnet on plaque number was studied. Additionally, for isolate 97P70, the effect on plaque size was investigated. Ganciclovir was most potent in reducing plaque number, followed by PMEDAP and acyclovir. Adefovir and cidofovir were less effective and foscarnet was the least effective compound. There were no differences detected for acyclovir, ganciclovir, adefovir and PMEDAP between the abortigenic and neuropathogenic isolates. One abortigenic isolate (99P96) was more susceptible to cidofovir and two neuropathogenic isolates (99P136 and 03P37) were less susceptible to foscarnet. For isolate 97P70, all compounds resulted in a significant reduction of plaque size. The most remarkable effect was observed for cidofovir. It was 40-fold more effective in reducing plaque size than in reducing plaque number. In conclusion, ganciclovir was the most potent compound and therefore, may be a valuable candidate for the treatment of EHV-1 infections in horses. The antiviral effect of foscarnet on plaque number was highly dependent on the viral isolate tested. Therefore, it is no valuable antiviral for the treatment of herpesvirus-infections. Cidofovir, although less effective in reducing plaque number, had a strong effect on plaque size. #

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Equine Herpesvirus Type 1 (EHV‐1) Myeloencephalopathy: a Case Report

Cited by 29 publications

References 26 publications

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a ⁺ Monocytic Cells upon Adhesion to Endothelial Cells

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a ⁺ Monocytic Cells upon Adhesion to Endothelial Cells

Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

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Equine Herpesvirus Type 1 (EHV‐1) Myeloencephalopathy: a Case Report

Cited by 29 publications

References 26 publications

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a + Monocytic Cells upon Adhesion to Endothelial Cells

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a + Monocytic Cells upon Adhesion to Endothelial Cells

Equine herpesvirus type 1 replication is delayed in CD172a+ monocytic cells and controlled by histone deacetylases

In vitro susceptibility of six isolates of equine herpesvirus 1 to acyclovir, ganciclovir, cidofovir, adefovir, PMEDAP and foscarnet

Contact Info

Product

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Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a ⁺ Monocytic Cells upon Adhesion to Endothelial Cells

Equine Herpesvirus Type 1 Enhances Viral Replication in CD172a ⁺ Monocytic Cells upon Adhesion to Endothelial Cells