Related Experiment Videos
Membrane related effects in endothelial cells induced by human cytomegalovirus
A G van Geelen1, M E Slobbe-van Drunen, A D Muller
1Department of Medical Microbiology, University Hospital of Maastricht, The Netherlands.
Abstract:
Previously, we have reported on the increase in procoagulant activity of human umbilical vein endothelial cells (HUVEC) after infection with human cytomegalovirus (HCMV). When using microvascular endothelial cells from foreskin (MVEC), we also observe a significant increase in membrane perturbation and a concomittant increase in procoagulant activity. This effect is both observed with a laboratory HCMV strain (AD169) with low pathogenicity for endothelium and a HUVEC adapted strain (VHL-E) that readily infects endothelial cells. We compared the membrane perturbation of two types of endothelial cells, HUVEC and MVEC with human embryonal fibroblasts (HEF), being fully permissive for both strains. A membrane effect was only found in endothelial cells. Our results suggest that HCMV induces in MVEC more merocyanine-540 incorporation in the membrane as in HUVEC. The increase in the procoagulant activity induced by HCMV was more pronounced in MVEC than in HUVEC. Inactivated virus, as well as virus pre-incubated with heparin was unable to evoke membrane perturbation. It therefore appears that HCMV induces a rapid membrane response in vascular endothelium and that physical interaction of the virion and the endothelial cell is required to elicit this response.
Insights
Human cytomegalovirus (HCMV) infection causes significant membrane changes and increases procoagulant activity in microvascular endothelial cells (MVEC). This rapid response in vascular endothelium requires direct virion-endothelial cell interaction.
Area of Science:
- Virology
- Cell Biology
- Immunology
Background:
- Human cytomegalovirus (HCMV) is a common pathogen with known effects on endothelial cells.
- Previous studies indicated HCMV increases procoagulant activity in human umbilical vein endothelial cells (HUVEC).
Purpose of the Study:
- To investigate HCMV-induced membrane perturbation and procoagulant activity in microvascular endothelial cells (MVEC).
- To compare these effects between MVEC and HUVEC.
- To determine the mechanism of HCMV-induced membrane response.
Main Methods:
- Infection of endothelial cells (HUVEC, MVEC) and human embryonal fibroblasts (HEF) with HCMV strains AD169 and VHL-E.
- Assessment of membrane perturbation using merocyanine-540 incorporation.
- Measurement of procoagulant activity.
- Use of inactivated virus and heparin-treated virus to assess interaction requirements.
Main Results:
- HCMV infection significantly increased membrane perturbation and procoagulant activity in MVEC, more so than in HUVEC.
- Membrane effects were specific to endothelial cells, not observed in HEF.
- HCMV induced greater merocyanine-540 incorporation in MVEC membranes compared to HUVEC.
- Inactivated or heparin-treated HCMV did not induce membrane perturbation.
Conclusions:
- HCMV rapidly alters the membrane of vascular endothelium, particularly MVEC.
- Physical interaction between the HCMV virion and endothelial cells is essential for this membrane response.
- The findings highlight a distinct endothelial cell response to HCMV infection, impacting vascular function.