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Equid herpesvirus type 1 activates platelets.

ABSTRACT: Equid herpesvirus type 1 (EHV-1) causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing ?-granule secretion (surface P-selectin expression) and platelet microvesiculation (increased small events double positive for CD41 and Annexin V). Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM). A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that ?-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis that occurs in clinically infected horses and provides a new mechanism by which viruses activate hemostasis.

SUBMITTER: Stokol T

PROVIDER: S-EPMC4407896 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Equid herpesvirus type 1 activates platelets.

Stokol Tracy T Yeo Wee Ming WM Burnett Deborah D DeAngelis Nicole N Huang Teng T Osterrieder Nikolaus N Catalfamo James J

PloS one 20150423 4

Equid herpesvirus type 1 (EHV-1) causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activ ...[more]

PMID: 25905776

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Project description:The risk of respiratory disease in the transported horse can increase as a consequence of immunosuppression and stress associated primarily with opportunistic bacterial proliferation and viral reactivation. This study examines the ecology of equid herpesviruses (EHV) in these horses, exploring reactivation and changes in infection and shedding associated with transport, and any potential contributions to transport-related respiratory disease. Twelve horses were subjected to an 8-h road-transport event. Antibodies to EHV-1 and EHV-4 were detected by ELISA in serum collected prior to, immediately after and 2 weeks post transport. Respiratory tract endoscopy and tracheal washes were collected prior to and 5 days after transportation. Nasal swabs collected prior to, immediately after, 1 and 5 days following transport were screened for EHV-1,-2,-4,-5 using qPCR. Six horses had persistent neutrophilic airway infiltrates post transportation, indicative of subclinical respiratory disease. No horses were qPCR positive for either of the alphaherpesviruses (i.e., EHV-1/-4) nor did any seroconvert to either virus. Four out of nine horses positive for either EHV-2 or EHV-5 on qPCR prior to transport developed neutrophilic airway inflammation. Five horses showed increasingly positive readings on qPCR (i.e., reduced Cq) for EHV-2 after transportation and seven out of eleven horses positive for EHV-2 after transport shared strains of high sequence similarity with other horses in the study. One EHV-2 virus detected in one horse after transport was genetically different which may be due to reactivation. The clinical significance of EHV-2 and EHV-5 remains in question. However these results indicate that transportation may lead to increased shedding, transmission and reactivation of EHV-2 and EHV-5 but not EHV-1/-4. Unlike previous work focusing on the role of alphaherpesviruses, this research suggests that investigation of the gammaherpesviruses (i.e., EHV-2/-5) in transport-related disease should not be dismissed, particularly given that these viruses can encode suppressive immunomodulators that may affect host health.

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Equid herpesvirus type 1 activates platelets.

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Equid herpesvirus type 1 activates platelets.

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