Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release
Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2015-03-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00220/full |
| _version_ | 1818620915192168448 |
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| author | Marco Goeijenbier Joost CM Meijers Joost CM Meijers Fatih Anfasa Fatih Anfasa Jeroen Roose Jeroen Roose Cornelia AM Van de Weg Kamran Bakhtiari Heikki Henttonen Antti Vaheri Albert Osterhaus Albert Osterhaus Eric C.M. Van Gorp Byron Emanuel Eusebio Martina Byron Emanuel Eusebio Martina |
| author_facet | Marco Goeijenbier Joost CM Meijers Joost CM Meijers Fatih Anfasa Fatih Anfasa Jeroen Roose Jeroen Roose Cornelia AM Van de Weg Kamran Bakhtiari Heikki Henttonen Antti Vaheri Albert Osterhaus Albert Osterhaus Eric C.M. Van Gorp Byron Emanuel Eusebio Martina Byron Emanuel Eusebio Martina |
| author_sort | Marco Goeijenbier |
| collection | DOAJ |
| description | Puumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis. |
| first_indexed | 2024-12-16T18:00:58Z |
| format | Article |
| id | doaj.art-f3bbcda9470b4094b69f9600400b2a97 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-16T18:00:58Z |
| publishDate | 2015-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-f3bbcda9470b4094b69f9600400b2a972022-12-21T22:22:04ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2015-03-01610.3389/fmicb.2015.00220134457Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator releaseMarco Goeijenbier0Joost CM Meijers1Joost CM Meijers2Fatih Anfasa3Fatih Anfasa4Jeroen Roose5Jeroen Roose6Cornelia AM Van de Weg7Kamran Bakhtiari8Heikki Henttonen9Antti Vaheri10Albert Osterhaus11Albert Osterhaus12Eric C.M. Van Gorp13Byron Emanuel Eusebio Martina14Byron Emanuel Eusebio Martina15Erasmus McAcademic Medical CenterSanquin ResearchErasmus McUniversitas IndonesiaErasmus McARTEMIS One Health Research InstituteErasmus McSanquin ResearchMetlaHaartman InstituteErasmus McARTEMIS One Health Research InstituteErasmus McErasmus McARTEMIS One Health Research InstitutePuumala virus (PUUV) infection causes over 5000 cases of hemorrhagic fever in Europe annually and can influence the hemostatic balance extensively. Infection might lead to hemorrhage, while a recent study showed an increased risk of myocardial infarction during or shortly after PUUV infection. The mechanism by which this hantavirus influences the coagulation system remains unknown. Therefore we aimed to elucidate mechanisms explaining alterations seen in primary and secondary hemostasis during PUUV infection. By using low passage PUUV isolates to infect primary human umbilical vein endothelial cells (HUVECs) we were able to show alterations in the regulation of primary- and secondary hemostasis and in the release of fibrinolysis regulators. Our main finding was an activation of secondary hemostasis due to increased tissue factor expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVECs and subsequently specifically to PUUV virus particles. Infection of HUVECs with PUUV did not result in increased von Willebrand factor while they produced more plasminogen activator inhibitor type-1 (PAI-1) compared to controls. The PAI-1 produced in this model formed complexes with vitronectin. This is the first report that reveals a potential mechanism behind the pro-coagulant changes in PUUV patients, which could be the result of increased thrombin generation due to an increased tissue factor expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00220/fullEndothelial CellsHantavirusHemorrhagic Fever with Renal SyndromeHemorrhagic Fevers, ViralHemostasisplatelets |
| spellingShingle | Marco Goeijenbier Joost CM Meijers Joost CM Meijers Fatih Anfasa Fatih Anfasa Jeroen Roose Jeroen Roose Cornelia AM Van de Weg Kamran Bakhtiari Heikki Henttonen Antti Vaheri Albert Osterhaus Albert Osterhaus Eric C.M. Van Gorp Byron Emanuel Eusebio Martina Byron Emanuel Eusebio Martina Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release Frontiers in Microbiology Endothelial Cells Hantavirus Hemorrhagic Fever with Renal Syndrome Hemorrhagic Fevers, Viral Hemostasis platelets |
| title | Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release |
| title_full | Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release |
| title_fullStr | Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release |
| title_full_unstemmed | Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release |
| title_short | Effect of Puumala hantavirus infection on Human Umbilical Vein Endothelial Cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release |
| title_sort | effect of puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function platelet interactions increased tissue factor expression and fibrinolysis regulator release |
| topic | Endothelial Cells Hantavirus Hemorrhagic Fever with Renal Syndrome Hemorrhagic Fevers, Viral Hemostasis platelets |
| url | http://journal.frontiersin.org/Journal/10.3389/fmicb.2015.00220/full |
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