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Journal of Virology, April 1999, p. 3491-3496, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Ebola Virus Selectively Inhibits Responses to Interferons, but Not to Interleukin-1beta , in Endothelial Cells

Brian H. Harcourt,1 Anthony Sanchez,2 and Margaret K. Offermann1,3,*

Program in Genetics and Molecular Biology1 and Winship Cancer Center and Division of Hematology and Oncology, Department of Internal Medicine,3 Emory University, Atlanta, Georgia 30322, and Special Pathogens Branch, Division of Viral and Rickettsial Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Atlanta, Georgia 303332

Received 9 October 1998/Accepted 21 December 1998

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

* Corresponding author. Mailing address: Winship Cancer Center, 1365 B Clifton Rd., Atlanta, GA 30322. Phone: (404) 778-5808. Fax: (404) 778-5016. E-mail: mofferm{at}emory.edu.

Journal of Virology, April 1999, p. 3491-3496, Vol. 73, No. 4
0022-538X/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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