Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release
Identifieur interne : 001093 ( Main/Exploration ); précédent : 001092; suivant : 001094Effect of Puumala hantavirus infection on human umbilical vein endothelial cell hemostatic function: platelet interactions, increased tissue factor expression and fibrinolysis regulator release
Auteurs : Marco Goeijenbier [Pays-Bas] ; Joost C. M. Meijers [Pays-Bas] ; Fatih Anfasa [Pays-Bas, Indonésie] ; Jeroen M. Roose [Pays-Bas] ; Cornelia A. M. Van De Weg [Pays-Bas] ; Kamran Bakhtiari [Pays-Bas] ; Heikki Henttonen [Finlande] ; Antti Vaheri [Finlande] ; Albert D. M. E. Osterhaus [Pays-Bas] ; Eric C. M. Van Gorp [Pays-Bas] ; Byron E. E. Martina [Pays-Bas]Source :
- Frontiers in Microbiology [ 1664-302X ] ; 2015.
Abstract
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 (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC 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 TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.
Url:
DOI: 10.3389/fmicb.2015.00220
PubMed: 25852676
PubMed Central: 4371750
Affiliations:
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M." last="Meijers">Joost C. M. Meijers</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam</institution><country>Amsterdam, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division ofOral Biology, College ofDentistry, The Ohio State University, Columbus, OH 43210</wicri:regionArea><wicri:noRegion>OH 43210</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Plasma Proteins, Sanquin Research, Amsterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Anfasa, Fatih" sort="Anfasa, Fatih" uniqKey="Anfasa F" first="Fatih" last="Anfasa">Fatih Anfasa</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Viroscience, Erasmus MC, Rotterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff4"><institution>Department of Internal Medicine, Faculty of Medicine, Universitas Indonesia</institution><country>Jakarta, Indonesia</country></nlm:aff><country xml:lang="fr">Indonésie</country><wicri:regionArea>Division ofOral Biology, College ofDentistry, The Ohio State University, Columbus, OH 43210</wicri:regionArea><wicri:noRegion>OH 43210</wicri:noRegion></affiliation></author><author><name sortKey="Roose, Jeroen M" sort="Roose, Jeroen M" uniqKey="Roose J" first="Jeroen M." last="Roose">Jeroen M. Roose</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Viroscience, Erasmus MC, Rotterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Artemis One Health Institute, Utrecht</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Van De Weg, Cornelia A M" sort="Van De Weg, Cornelia A M" uniqKey="Van De Weg C" first="Cornelia A. M." last="Van De Weg">Cornelia A. M. Van De Weg</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Viroscience, Erasmus MC, Rotterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Bakhtiari, Kamran" sort="Bakhtiari, Kamran" uniqKey="Bakhtiari K" first="Kamran" last="Bakhtiari">Kamran Bakhtiari</name><affiliation wicri:level="1"><nlm:aff id="aff2"><institution>Department of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam</institution><country>Amsterdam, Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea>Division ofOral Biology, College ofDentistry, The Ohio State University, Columbus, OH 43210</wicri:regionArea><wicri:noRegion>OH 43210</wicri:noRegion></affiliation><affiliation wicri:level="1"><nlm:aff id="aff3"><institution>Department of Plasma Proteins, Sanquin Research, Amsterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Henttonen, Heikki" sort="Henttonen, Heikki" uniqKey="Henttonen H" first="Heikki" last="Henttonen">Heikki Henttonen</name><affiliation wicri:level="1"><nlm:aff id="aff6"><institution>Metla, Finnish Forest Research Institute, Vantaa</institution><country>Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Vaheri, Antti" sort="Vaheri, Antti" uniqKey="Vaheri A" first="Antti" last="Vaheri">Antti Vaheri</name><affiliation wicri:level="1"><nlm:aff id="aff7"><institution>Department of Virology, Haartman Institute, University Of Helsinki</institution><country>Helsinki, Finland</country></nlm:aff><country xml:lang="fr">Finlande</country><wicri:regionArea>Division ofOral Biology, College ofDentistry, The Ohio State University, Columbus, OH 43210</wicri:regionArea><wicri:noRegion>OH 43210</wicri:noRegion></affiliation></author><author><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Viroscience, Erasmus MC, Rotterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Artemis One Health Institute, Utrecht</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Van Gorp, Eric C M" sort="Van Gorp, Eric C M" uniqKey="Van Gorp E" first="Eric C. M." last="Van Gorp">Eric C. M. Van Gorp</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Viroscience, Erasmus MC, Rotterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author><author><name sortKey="Martina, Byron E E" sort="Martina, Byron E E" uniqKey="Martina B" first="Byron E. E." last="Martina">Byron E. E. Martina</name><affiliation wicri:level="1"><nlm:aff id="aff1"><institution>Department of Viroscience, Erasmus MC, Rotterdam</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation><affiliation wicri:level="1"><nlm:aff id="aff5"><institution>Artemis One Health Institute, Utrecht</institution><country>Netherlands</country></nlm:aff><country xml:lang="fr">Pays-Bas</country><wicri:regionArea># see nlm:aff country strict</wicri:regionArea></affiliation></author></analytic><series><title level="j">Frontiers in Microbiology</title><idno type="eISSN">1664-302X</idno><imprint><date when="2015">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><p>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 (TF) expression leading to increased thrombin generation in a functional assay. Furthermore, we showed that during infection platelets adhered to HUVEC and subsequently specifically to PUUV virus particles. Infection of HUVEC 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 TF expression on endothelial cells during infection. Furthermore, we provide insight into the contribution of endothelial cell responses regarding hemostasis in PUUV pathogenesis.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Antonen, J" uniqKey="Antonen J">J. Antonen</name></author><author><name sortKey="Leppanen, I" uniqKey="Leppanen I">I. Leppanen</name></author><author><name sortKey="Tenhunen, J" uniqKey="Tenhunen J">J. Tenhunen</name></author><author><name sortKey="Arvola, P" uniqKey="Arvola P">P. 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E." last="Martina">Byron E. E. Martina</name><name sortKey="Meijers, Joost C M" sort="Meijers, Joost C M" uniqKey="Meijers J" first="Joost C. M." last="Meijers">Joost C. M. Meijers</name><name sortKey="Meijers, Joost C M" sort="Meijers, Joost C M" uniqKey="Meijers J" first="Joost C. M." last="Meijers">Joost C. M. Meijers</name><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><name sortKey="Osterhaus, Albert D M E" sort="Osterhaus, Albert D M E" uniqKey="Osterhaus A" first="Albert D. M. E." last="Osterhaus">Albert D. M. E. Osterhaus</name><name sortKey="Roose, Jeroen M" sort="Roose, Jeroen M" uniqKey="Roose J" first="Jeroen M." last="Roose">Jeroen M. Roose</name><name sortKey="Roose, Jeroen M" sort="Roose, Jeroen M" uniqKey="Roose J" first="Jeroen M." last="Roose">Jeroen M. Roose</name><name sortKey="Van De Weg, Cornelia A M" sort="Van De Weg, Cornelia A M" uniqKey="Van De Weg C" first="Cornelia A. M." last="Van De Weg">Cornelia A. M. Van De Weg</name><name sortKey="Van Gorp, Eric C M" sort="Van Gorp, Eric C M" uniqKey="Van Gorp E" first="Eric C. M." last="Van Gorp">Eric C. M. Van Gorp</name></country><country name="Indonésie"><noRegion><name sortKey="Anfasa, Fatih" sort="Anfasa, Fatih" uniqKey="Anfasa F" first="Fatih" last="Anfasa">Fatih Anfasa</name></noRegion></country><country name="Finlande"><noRegion><name sortKey="Henttonen, Heikki" sort="Henttonen, Heikki" uniqKey="Henttonen H" first="Heikki" last="Henttonen">Heikki Henttonen</name></noRegion><name sortKey="Vaheri, Antti" sort="Vaheri, Antti" uniqKey="Vaheri A" first="Antti" last="Vaheri">Antti Vaheri</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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