Equine alphaherpesviruses (EHV-1 and EHV-4) differ in their efficiency to infect mononuclear cells during early steps of infection in nasal mucosal explants

Vandekerckhove, Annelies; Glorieux, Sarah; Gryspeerdt, Annick; Steukers, Lennert; Doorsselaere, Jan Van; Osterrieder, Nikolaus; Walle, Gerlinde R. Van de; Nauwynck, Hans

doi:10.1016/j.vetmic.2011.03.038

Cited by 35 publications

(32 citation statements)

References 43 publications

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“…We thus infected monocytes with EHV-4 at an MOI of 5. We chose EHV-4 because this virus does infect PBMC [43] and mononuclear cells in nasal explants [44] in vitro but is not associated with thrombosis in vivo. We found that EHV-4 did induce procoagulant activity in equine monocytes and that this activity was also dependent on exogenous FVIIa (data not shown), however the response was significantly lower than that observed with EHV-1 and was similar to that seen with UV-inactivated EHV-1.…”

Section: Resultsmentioning

confidence: 99%

“…These strain-dependent differences were not attributable to the D 752 polymorphism in the DNA polymerase. This polymorphism has been strongly associated with neuropathogenicity [25,27,32,33], possibly due to a leukocyte-associated viremia of higher magnitude and longer duration [25,27] or more efficient infection of CD172-positive mononuclear cells after invasion through the respiratory mucosa [2,29,44]. Interestingly, the D 752 polymorphism in the virus DNA polymerase did affect the maximal procoagulant response induced by RacL11 but not by Ab4.…”

Section: Discussionmentioning

confidence: 99%

“…The effect was partly replication-dependent in the case of EHV-1, but not with EHV-4, as shown by inhibition with UV light inactivation of the virus and aphidicolin treatment of infected cells. EHV-4 does not appear to efficiently replicate in monocytes [43,44], which may explain the lack of replication-dependent procoagulant activity with this virus. However, since procoagulant activity independent of virus replication was seen with both viruses, early events such as virus attachment, entry or intracellular trafficking, appear sufficient to induce this response and may even be required for the maximal procoagulant activity that is induced by replication with EHV-1.…”

Section: Discussionmentioning

confidence: 99%

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Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes

Yeo

Osterrieder

Stokol

2013

Vet Res

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The alphaherpesvirus, equine herpesvirus type 1 (EHV-1), is a highly prevalent cause of equine infectious abortion and encephalomyelopathy. These syndromes have been attributed to ischemic necrosis from thrombosis in placental and neural vessels, although the mechanisms underlying thrombosis are unknown. After inhalation, EHV-1 establishes a peripheral blood mononuclear cell-associated viremia, with monocytes being a target of infection. Monocytes are also the main source of tissue factor (TF) in diseased states. Since TF is the primary activator of coagulation, increased monocyte TF expression could be involved in EHV-1-associated thrombosis. We hypothesized that EHV-1 infection would induce TF-dependent procoagulant activity in equine monocytes. Monocyte-enriched fractions of blood were infected with abortigenic (RacL11, NY03) and neuropathogenic (Ab4) EHV-1 strains. All strains induced procoagulant activity, to variable degrees, within 1 to 4 h, with maximal activity at 24 h, after infection. Virus-induced procoagulant activity was similar to that seen with lipopolysaccharide, a known stimulant of TF-mediated procoagulant responses. Virus-induced procoagulant activity was factor VIIa-dependent and temporally associated with TF gene transcription, implicating TF as the main driver of the activity. Procoagulant activity was mildly decreased (30-40%) when virus was inactivated by ultraviolet light or when infected cells were treated with aphidicolin, a virus DNA polymerase inhibitor, suggesting early events of virus infection (attachment, entry or intracellular trafficking) are the primary stimulus of procoagulant activity. Our results indicate that EHV-1 rapidly stimulates procoagulant activity in equine monocytes in vitro. The EHV-1-induced procoagulant activity in monocytes may contribute to clinical thrombosis in horses with EHV-1 infection.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes

Yeo

Osterrieder

Stokol

2013

Vet Res

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“…By using these explants, invasion processes of different alphaherpesviruses (EHV1, EHV4, BHV1, SHV1 and HSV1) have already been described. Based on their invasion mechanism, alphaherpesviruses can be classified into three types: EHV4 shows replication in the respiratory epithelial cells without invasion through the BM; BHV1, SHV1 and HSV1 exhibit a plaquewise spread through the BM in the in vitro explant model; and EHV1 spreads only laterally and does not breach the BM (similar to EHV4), but invades deeper tissues of the respiratory tract via infected leukocytes that function as Trojan horses Vandekerckhove et al, 2010Vandekerckhove et al, , 2011Glorieux et al, 2011;Steukers et al, 2012).…”

Section: Discussionmentioning

confidence: 99%

Replication characteristics of infectious laryngotracheitis virus in the respiratory and conjunctival mucosa

Reddy

Steukers

et al. 2014

Avian Pathology

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Avian infectious laryngotracheitis virus (ILTV) is an alphaherpesvirus of poultry that is spread worldwide. ILTV enters its host via the respiratory tract and the eyes. Although ILTV has been known for a long time, the replication characteristics of the virus in the respiratory and conjunctival mucosa are still poorly studied. To study these characteristics, two in vitro explant models were developed. Light microscopy and fluorescent terminal deoxynucleotidyl transferase dUTP nick end-labelling staining were used to evaluate the viability of mucosal explants, which were found to be viable up to the end of the experiment at 96 h of cultivation. The tracheal and conjunctival mucosal explants were inoculated with ILTV and collected at 0, 24, 48 and 72 h post inoculation (p.i.). ILTV spread in a plaque-wise manner in both mucosae. A reproducible quantitative analysis of this mucosal spread was evaluated by measuring plaque numbers, plaque latitude and invasion depth underneath the basement membrane. No major differences in plaque numbers were observed over time. Plaque latitude progressively increased to 70.4 ± 12.9 μm in the trachea and 97.8 ± 9.5 μm in the conjunctiva at 72 h p.i. The virus had difficulty crossing the basement membrane and was first observed only at 48 h p.i. The virus was observed at 72 h p.i. in 56% (trachea) and 74% (conjunctiva) of the plaques. Viability analysis of infected explants indicated that ILTV blocks apoptosis in infected cells of both mucosae but activates apoptosis in bystander cells.

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“…Tissues of the deep intranasal part of the septum were collected from horses between 4 and 7 years old at the slaughterhouse and transported to the laboratory as described previously (Vandekerckhove et al, 2011). The isolation of equine nasal mucosal CD172a…”

Section: Isolation Of Equine Nasal Mucosal Cd172amentioning

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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Equine alphaherpesviruses (EHV-1 and EHV-4) differ in their efficiency to infect mononuclear cells during early steps of infection in nasal mucosal explants

Cited by 35 publications

References 43 publications

Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes

Equine herpesvirus type 1 infection induces procoagulant activity in equine monocytes

Replication characteristics of infectious laryngotracheitis virus in the respiratory and conjunctival mucosa

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

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