The effect of measles virus and Ebola virus on the innate immune response of endothelial cells

The vascular endothelium plays an important role in the host's immune response during viral infection through the expression of immunomodulatory genes such as cellular adhesion molecules, cytokines, PKR, 2' -5'(A)N and MHC I. These genes are either induced directly by viruses or are induced by cytokines such as Type I IFN, Type II IFN and IL-1beta.;We demonstrate that infection of human umbilical vein endothelial cells (HUVECs) with the RNA viruses, measles or Ebola, led to profoundly different states of immunomodulatory gene induction. Infection of HUVECs with multiple strains of measles virus led to the induction of ICAM-1, IL-6, IL-1beta and MHC I. The induction was not dependent on protein synthesis and correlated with the activation of the latent transcription factor NF-kappaB.;In contrast to measles, infection of HUVECs with Ebola did not result in immunomodulatory or antiviral gene induction and suppressed the cell's ability to respond to exogenous IFN-alpha, IFN-gamma or the synthetic double-stranded RNA (dsRNA), poly I:poly C. However, gene induction by IL-1beta was not suppressed by infection with Ebola, suggesting that the inhibition of IFN and dsRNA signaling is specific. In addition, infection with Ebola blocked the induction by IFNs and dsRNA of nuclear proteins that bind to the interferon regulatory elements found in the promoters of IFN-inducible genes.;The immune response to these viruses during the course of natural infection are very different. Patients with measles virus have extensive leukocyte infiltration into infected areas and they generate a strong humoral and cell-mediated immune response. In contrast, in fatal cases of Ebola, patients die with high viremia, little evidence of leukocyte infiltration into infected areas, and little evidence of a humoral or cell-mediated immune response. The ability of measles to induce immunomodulatory genes in endothelial cells may be important in the effective immune response seen during infection with the virus. However, Ebola's ability to infect endothelial cells, to produce prodigious amounts of progeny virions without inducing immunomodulatory genes and to block the cell's ability to respond to IFN could play an important role in the severe immunosuppression and pathogenecity of disease caused by Ebola infection.