Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells
Zika virus (ZIKV) infection is typically characterized by a mild disease presenting with fever, maculopapular rash, headache, fatigue, myalgia, and arthralgia. A recent animal study found that ZIKV-infected pregnant Ifnar−/−mice developed vascular damage in the placenta and reduced amount of fetal c...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2019-04-01
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| Series: | Frontiers in Microbiology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fmicb.2019.00817/full |
| _version_ | 1818911955166953472 |
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| author | Fatih Anfasa Fatih Anfasa Marco Goeijenbier Marco Goeijenbier Widagdo Widagdo Jurre Y. Siegers Noreen Mumtaz Nisreen Okba Debby van Riel Barry Rockx Marion P. G. Koopmans Joost C. M. Meijers Joost C. M. Meijers Byron E. E. Martina Byron E. E. Martina |
| author_facet | Fatih Anfasa Fatih Anfasa Marco Goeijenbier Marco Goeijenbier Widagdo Widagdo Jurre Y. Siegers Noreen Mumtaz Nisreen Okba Debby van Riel Barry Rockx Marion P. G. Koopmans Joost C. M. Meijers Joost C. M. Meijers Byron E. E. Martina Byron E. E. Martina |
| author_sort | Fatih Anfasa |
| collection | DOAJ |
| description | Zika virus (ZIKV) infection is typically characterized by a mild disease presenting with fever, maculopapular rash, headache, fatigue, myalgia, and arthralgia. A recent animal study found that ZIKV-infected pregnant Ifnar−/−mice developed vascular damage in the placenta and reduced amount of fetal capillaries. Moreover, ZIKV infection causes segmental thrombosis in the umbilical cord of pregnant rhesus macaques. Furthermore, several case reports suggest that ZIKV infection cause coagulation disorders. These results suggest that ZIKV could cause an alteration in the host hemostatic response, however, the mechanism has not been investigated thus far. This paper aims to determine whether ZIKV infection on HUVECs induces apoptosis and elevation of tissue factor (TF) that leads to activation of secondary hemostasis. We infected HUVECs with two ZIKV strains and performed virus titration, immunostaining, and flow cytometry to confirm and quantify infection. We measured TF concentrations with flow cytometry and performed thrombin generation test (TGT) as a functional assay to assess secondary hemostasis. Furthermore, we determined the amount of cell death using flow cytometry. We also performed enzyme-linked immunosorbent assay (ELISA) to determine interleukin (IL)-6 and IL-8 production and conducted blocking experiments to associate these cytokines with TF expression. Both ZIKV strains infected and replicated to high titers in HUVECs. We found that infection induced elevation of TF expressions. We also showed that increased TF expression led to shortened TGT time. Moreover, the data revealed that infection induced apoptosis. In addition, there was a significant increase of IL-6 and IL-8 production in infected cells. Here we provide in vitro evidence that infection of HUVECs with ZIKV induces apoptosis and elevation of TF expression that leads to activation of secondary hemostasis. |
| first_indexed | 2024-12-19T23:06:55Z |
| format | Article |
| id | doaj.art-39e047cf495a46cd87c62a773838a5a4 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-19T23:06:55Z |
| publishDate | 2019-04-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-39e047cf495a46cd87c62a773838a5a42022-12-21T20:02:21ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2019-04-011010.3389/fmicb.2019.00817418877Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial CellsFatih Anfasa0Fatih Anfasa1Marco Goeijenbier2Marco Goeijenbier3Widagdo Widagdo4Jurre Y. Siegers5Noreen Mumtaz6Nisreen Okba7Debby van Riel8Barry Rockx9Marion P. G. Koopmans10Joost C. M. Meijers11Joost C. M. Meijers12Byron E. E. Martina13Byron E. E. Martina14Department of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsFaculty of Medicine, Universitas Indonesia, Jakarta, IndonesiaDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Internal Medicine, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsDepartment of Plasma Proteins, Sanquin Research, Amsterdam, NetherlandsDepartment of Experimental Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, NetherlandsDepartment of Viroscience, Erasmus University Medical Center, Rotterdam, NetherlandsArtemis One Health Research Institute, Delft, NetherlandsZika virus (ZIKV) infection is typically characterized by a mild disease presenting with fever, maculopapular rash, headache, fatigue, myalgia, and arthralgia. A recent animal study found that ZIKV-infected pregnant Ifnar−/−mice developed vascular damage in the placenta and reduced amount of fetal capillaries. Moreover, ZIKV infection causes segmental thrombosis in the umbilical cord of pregnant rhesus macaques. Furthermore, several case reports suggest that ZIKV infection cause coagulation disorders. These results suggest that ZIKV could cause an alteration in the host hemostatic response, however, the mechanism has not been investigated thus far. This paper aims to determine whether ZIKV infection on HUVECs induces apoptosis and elevation of tissue factor (TF) that leads to activation of secondary hemostasis. We infected HUVECs with two ZIKV strains and performed virus titration, immunostaining, and flow cytometry to confirm and quantify infection. We measured TF concentrations with flow cytometry and performed thrombin generation test (TGT) as a functional assay to assess secondary hemostasis. Furthermore, we determined the amount of cell death using flow cytometry. We also performed enzyme-linked immunosorbent assay (ELISA) to determine interleukin (IL)-6 and IL-8 production and conducted blocking experiments to associate these cytokines with TF expression. Both ZIKV strains infected and replicated to high titers in HUVECs. We found that infection induced elevation of TF expressions. We also showed that increased TF expression led to shortened TGT time. Moreover, the data revealed that infection induced apoptosis. In addition, there was a significant increase of IL-6 and IL-8 production in infected cells. Here we provide in vitro evidence that infection of HUVECs with ZIKV induces apoptosis and elevation of TF expression that leads to activation of secondary hemostasis.https://www.frontiersin.org/article/10.3389/fmicb.2019.00817/fullZika virusendothelial cellsHUVECstissue factorsecondary hemostasisapoptosis |
| spellingShingle | Fatih Anfasa Fatih Anfasa Marco Goeijenbier Marco Goeijenbier Widagdo Widagdo Jurre Y. Siegers Noreen Mumtaz Nisreen Okba Debby van Riel Barry Rockx Marion P. G. Koopmans Joost C. M. Meijers Joost C. M. Meijers Byron E. E. Martina Byron E. E. Martina Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells Frontiers in Microbiology Zika virus endothelial cells HUVECs tissue factor secondary hemostasis apoptosis |
| title | Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells |
| title_full | Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells |
| title_fullStr | Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells |
| title_full_unstemmed | Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells |
| title_short | Zika Virus Infection Induces Elevation of Tissue Factor Production and Apoptosis on Human Umbilical Vein Endothelial Cells |
| title_sort | zika virus infection induces elevation of tissue factor production and apoptosis on human umbilical vein endothelial cells |
| topic | Zika virus endothelial cells HUVECs tissue factor secondary hemostasis apoptosis |
| url | https://www.frontiersin.org/article/10.3389/fmicb.2019.00817/full |
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