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The American Journal of Pathology logoLink to The American Journal of Pathology
. 1989 Jan;134(1):223–230.

Herpes simplex virus inhibits endothelial cell attachment and migration to extracellular matrix proteins.

M R Visser 1, G M Vercellotti 1, J B McCarthy 1, J L Goodman 1, T J Herbst 1, L T Furcht 1, H S Jacob 1
PMCID: PMC1879552  PMID: 2536523

Abstract

Herpes simplex virus (HSV) infection may be involved in various endothelial-injury syndromes, including vasculitis and atherosclerosis. In a previous study, it was reported that HSV-infected human umbilical endothelial cells are more vulnerable to detachment mediated by granulocyte-secreted proteases. To elucidate the molecular basis of this observation, the authors examined the interaction of infected endothelial cells with the purified basement membrane proteins, fibronectin, laminin, and type IV collagen. HSV-infected endothelial cells exhibited defects in their ability to adhere, spread, and migrate on all three matrix components. This defective adhesion could be partially overcome by increasing concentrations of fibronectin; in contrast, no abrogation of deficient binding occurs with increased levels of laminin or collagen type IV. This suggests that endothelial cells may use different surface constituents for binding to the three proteins and use multiple "receptors" for adhesion to the fibronectin molecule--"receptors" that are variably affected by HSV infection. The authors investigated this supposition by assaying adhesion of normal and infected endothelial cells to two non-overlapping cell-adhesion promoting fragments of fibronectin: 1) a 75 kd motility-promoting fragment which contains the arginyl-glycyl-aspartylserine (RGDS) adhesion sequence, and 2) a 33 kd carboxyl-terminal heparin binding fragment, which promotes cell adhesion by an RGDS-independent mechanism. Normal endothelial cells adhered and spread on both purified fragments. In contrast, while infected endothelial cells could adhere, albeit rather poorly, to high coating concentrations of the 75 kd fragment, these cells did not bind to the 33 kd heparin binding fragment of fibronectin at all. These results support the concept that endothelial cells adhere to multiple domains of fibronectin, and that HSV infection preferentially abrogates binding to the heparin-binding domain, while leaving relatively intact receptors for the RGDS-containing domain. In support, soluble RGDS significantly blocked fibronectin adhesion of infected, but not control, endothelial cells. It is concluded that HSV infection inhibits the interaction of endothelial cells with basement membrane proteins and weakens their tethering to substratum. This tethering is inadequate for proper cell spreading or movement to occur and may result in both excessive endothelial lift-off and impaired vascular repair in HSV infections.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

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