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Journal of Virology, January 2007, p. 182-192, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01006-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

The VP35 Protein of Ebola Virus Inhibits the Antiviral Effect Mediated by Double-Stranded RNA-Dependent Protein Kinase PKR{triangledown}

Zongdi Feng,{dagger} Melissa Cerveny,{dagger} Zhipeng Yan, and Bin He*

Department of Microbiology and Immunology, College of Medicine, The University of Illinois at Chicago, Chicago, Illinois 60612

Received 16 May 2006/ Accepted 9 October 2006

The VP35 protein of Ebola virus is a viral antagonist of interferon. It acts to block virus or double-stranded RNA-mediated activation of interferon regulatory factor 3, a transcription factor that facilitates the expression of interferon and interferon-stimulated genes. In this report, we show that the VP35 protein is also able to inhibit the antiviral response induced by alpha interferon. This depends on the VP35 function that interferes with the pathway regulated by double-stranded RNA-dependent protein kinase PKR. When expressed in a heterologous system, the VP35 protein enhanced viral polypeptide synthesis and growth in Vero cells pretreated with alpha/beta interferon, displaying an interferon-resistant phenotype. In correlation, phosphorylation of PKR and eIF-2{alpha} was suppressed in cells expressing the VP35 protein. This activity of the VP35 protein was required for efficient viral replication in PKR+/+ but not PKR–/– mouse embryo fibroblasts. Furthermore, VP35 appears to be a RNA binding protein. Notably, a deletion of amino acids 1 to 200, but not R312A substitution in the RNA binding motif, abolished the ability of the VP35 protein to confer viral resistance to interferon. However, the R312A substitution rendered the VP35 protein unable to inhibit the induction of the beta interferon promoter mediated by virus infection. Together, these results show that the VP35 protein targets multiple pathways of the interferon system.

* Corresponding author. Mailing address: Department of Microbiology and Immunology (M/C 790), College of Medicine, The University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612. Phone: (312) 996-2391. Fax: (312) 996-6415. E-mail: tshuo{at}uic.edu.

{triangledown} Published ahead of print on 25 October 2006.

{dagger} These authors contributed equally to this work.

Journal of Virology, January 2007, p. 182-192, Vol. 81, No. 1
0022-538X/07/$08.00+0     doi:10.1128/JVI.01006-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.



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