Procoagulant activity of endothelial cells after infection with respiratory viruses

Influenza virus epidemics are associated with excess mortality due to cardi ovascular diseases. There are several case reports of excessive coagulation during generalised influenza virus infection. In this study, we demonstrat e the ability of respiratory viruses (influenza A, influenza B, parainfluen za-1, respiratory syncytial virus, adenovirus, cytomegalovirus) to infect l ung fibroblasts and human umbilical vein endothelial cells in culture. All viral pathogens induced procoagulant activity in infected endothelial cells , as determined in a one-stage clotting assay, by causing an average 55% re duction in the clotting time. When factor VII deficient plasma was used clo tting time was not reduced. The induction of procoagulant activity was asso ciated with a 4- to 5-fold increase in the expression of tissue factor, as measured by the generation of factor Xa. Both experiments indicate that the procoagulant activity of endothelial cells in response to infection with r espiratory viruses is caused by upregulation of the extrinsic pathway. Alth ough both enveloped viruses and a non-enveloped virus (adenovirus) induced procoagulant activity in endothelial cells by stimulating tissue factor exp ression, the role of the viral envelope in the assembly of the prothrombina se complex remains uncertain. We conclude that both enveloped and non-enveloped respiratory viruses are c apable of infecting cultured human endothelial cells and causing a shift fr om anticoagulant to procoagulant activity associated with the induction of tissue factor expression.