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PMID: 17065211 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

The VP35 protein of Ebola virus inhibits the antiviral effect mediated by double-stranded RNA-dependent protein kinase PKR.

Journal of virology ·Vol. 81 ·No. 1 ·2007-01-00 ·Pages 182-92

Feng Z, Cerveny M, Yan Z, He B

Abstract

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-2alpha 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.

MeSH Terms
Animals Cells, Cultured Chlorocebus aethiops Ebolavirus/pathogenicity,physiology Humans Interferon-alpha/antagonists & inhibitors,metabolism Interferon-beta/antagonists & inhibitors,metabolism Mice Mutation Phosphorylation RNA, Double-Stranded/metabolism Sequence Analysis, Protein Vero Cells Viral Proteins/chemistry,genetics,physiology Viral Regulatory and Accessory Proteins Virus Replication eIF-2 Kinase/antagonists & inhibitors,metabolism
Chemicals
Interferon-alpha RNA, Double-Stranded VP35 protein, filovirus Viral Proteins Viral Regulatory and Accessory Proteins Interferon-beta eIF-2 Kinase
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Feng Zongdi
Department of Microbiology and Immunology (M/C 790), College of Medicine, The University of Illinois at Chicago, 835 South Wolcott Avenue, Chicago, IL 60612, USA.
Cerveny Melissa
Yan Zhipeng
He Bin
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.01006-06
Published
2007-01-00
Epub
2006-00-25
Pages
182-92
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC1797262
Subset
IM
Grants
NIAID NIH HHS · R21 AI053386 · United States
NIAID NIH HHS · AI 053386 · United States
External Links
PubMed source DOI: 10.1128/JVI.01006-06 PMC Full Text View journal details
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