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Journal of Virology, September 2009, p. 8993-8997, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00523-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Ebola Virus VP35 Antagonizes PKR Activity through Its C-Terminal Interferon Inhibitory Domain{triangledown}

Michael Schümann,1 Thorsten Gantke,1,{dagger} and Elke Mühlberger1,2,3*

Department of Virology, Philipps University Marburg, Hans-Meerwein-Straße 2, 35043 Marburg, Germany,1 National Emerging Infectious Diseases Laboratories Institute,2 Department of Microbiology, Boston University School of Medicine, 72 East Concord Street, Boston, Massachusetts 021183

Received 13 March 2009/ Accepted 2 June 2009

Ebola virus VP35 contains a C-terminal cluster of basic amino acids required for double-stranded RNA (dsRNA) binding and inhibition of interferon regulatory factor 3 (IRF3). VP35 also blocks protein kinase R (PKR) activation; however, the responsible domain has remained undefined. Here we show that the IRF inhibitory domain of VP35 mediates the inhibition of PKR and enhances the synthesis of coexpressed proteins. In contrast to dsRNA binding and IRF inhibition, alanine substitutions of at least two basic amino acids are required to abrogate PKR inhibition and enhanced protein expression. Moreover, we show that PKR activation is not only blocked but reversed by Ebola virus infection.

* Corresponding author. Mailing address: Department of Microbiology, Boston University School of Medicine, 72 East Concord Street, Boston, MA 02118. Phone: (617) 638-0336. Fax: (617) 638-4286. E-mail: muehlber{at}bu.edu

{triangledown} Published ahead of print on 10 June 2009.

{dagger} Present address: National Institute of Medical Research, The Ridgeway, Mill Hill, London, United Kingdom.

Journal of Virology, September 2009, p. 8993-8997, Vol. 83, No. 17
0022-538X/09/$08.00+0     doi:10.1128/JVI.00523-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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