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Equid Herpesvirus Type 1 Activates Platelets

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 am...

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Autores principales: Stokol, Tracy, Yeo, Wee Ming, Burnett, Deborah, DeAngelis, Nicole, Huang, Teng, Osterrieder, Nikolaus, Catalfamo, James
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407896/
https://www.ncbi.nlm.nih.gov/pubmed/25905776
http://dx.doi.org/10.1371/journal.pone.0122640
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author Stokol, Tracy
Yeo, Wee Ming
Burnett, Deborah
DeAngelis, Nicole
Huang, Teng
Osterrieder, Nikolaus
Catalfamo, James
author_facet Stokol, Tracy
Yeo, Wee Ming
Burnett, Deborah
DeAngelis, Nicole
Huang, Teng
Osterrieder, Nikolaus
Catalfamo, James
author_sort Stokol, Tracy
collection PubMed
description 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 α-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 α-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.
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spelling pubmed-44078962015-05-04 Equid Herpesvirus Type 1 Activates Platelets Stokol, Tracy Yeo, Wee Ming Burnett, Deborah DeAngelis, Nicole Huang, Teng Osterrieder, Nikolaus Catalfamo, James PLoS One Research Article 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 α-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 α-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. Public Library of Science 2015-04-23 /pmc/articles/PMC4407896/ /pubmed/25905776 http://dx.doi.org/10.1371/journal.pone.0122640 Text en © 2015 Stokol et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Stokol, Tracy
Yeo, Wee Ming
Burnett, Deborah
DeAngelis, Nicole
Huang, Teng
Osterrieder, Nikolaus
Catalfamo, James
Equid Herpesvirus Type 1 Activates Platelets
title Equid Herpesvirus Type 1 Activates Platelets
title_full Equid Herpesvirus Type 1 Activates Platelets
title_fullStr Equid Herpesvirus Type 1 Activates Platelets
title_full_unstemmed Equid Herpesvirus Type 1 Activates Platelets
title_short Equid Herpesvirus Type 1 Activates Platelets
title_sort equid herpesvirus type 1 activates platelets
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4407896/
https://www.ncbi.nlm.nih.gov/pubmed/25905776
http://dx.doi.org/10.1371/journal.pone.0122640
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