Ebola virus selectively inhibits responses to interferons, but not to Interleukin-1 beta, in endothelial cells

Ebola virus infection is highly lethal and leads to severe immunosuppressio n. In this study, we demonstrate that infection of human umbilical vein end othelial cells (HUVECs) with Ebola virus Zaire (EZ) suppressed basal expres sion of the major histocompatibility complex class I (MHC I) family of prot eins and inhibited the induction of multiple genes by alpha interferon (IFN -alpha) and IFN-gamma, including those coding for MHC I proteins, 2'-5' oli goadenylate synthetase [2'-5'(A)(N)], and IFN regulatory factor 1 (IRF-1). Induction of interleukin-6 (IL-6) and ICAM-1 by IL-1 beta was not suppresse d by infection with EZ, suggesting that the inhibition of IFN signaling is specific. Gel shift analysis demonstrated that infection with EZ blocked th e induction by IFNs of nuclear proteins that bind to IFN-stimulated respons e elements, gamma activation sequences, and IFN regulatory factor binding s ite (IRF-E). In contrast, infection with EZ did not block activation of the transcription factor NF-kappa B by IL-1 beta. The events that lead to the blockage of IFN signaling may be critical for Ebola virus-induced immunosup pression and would play a role in the pathogenesis of Ebola virus infection .