The Ebola virus VP35 protein is a suppressor of RNA silencing

J. Haasnoot, W. de Vries, E.J. Geutjes, M.W. Prins, P. de Haan, B. Berkhout

Research output: Contribution to journalArticleAcademicpeer-review

259 Citations (Scopus)

Abstract

RNA silencing or interference (RNAi) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of microRNAs. RNAi also serves as an innate antiviral defence response in plants, nematodes, and insects. This antiviral response is triggered by virus-specific double-stranded RNA molecules (dsRNAs) that are produced during infection. To overcome antiviral RNAi responses, many plant and insect viruses encode RNA silencing suppressors (RSSs) that enable them to replicate at higher titers. Recently, several human viruses were shown to encode RSSs, suggesting that RNAi also serves as an innate defence response in mammals. Here, we demonstrate that the Ebola virus VP35 protein is a suppressor of RNAi in mammalian cells and that its RSS activity is functionally equivalent to that of the HIV-1 Tat protein. We show that VP35 can replace HIV-1 Tat and thereby support the replication of a Tat-minus HIV-1 variant. The VP35 dsRNA-binding domain is required for this RSS activity. Vaccinia virus E3L protein and influenza A virus NS1 protein are also capable of replacing the HIV-1 Tat RSS function. These findings support the hypothesis that RNAi is part of the innate antiviral response in mammalian cells. Moreover, the results indicate that RSSs play a critical role in mammalian virus replication.
Original languageEnglish
Article numbere86
JournalPLoS Pathogens
Volume3
Issue number6
DOIs
Publication statusPublished - 2007

Keywords

  • double-stranded-rna
  • human-immunodeficiency-virus
  • influenza-a virus
  • small interfering rnas
  • hepatitis-c virus
  • ns1 protein
  • caenorhabditis-elegans
  • antiviral defense
  • vaccinia virus
  • type-1 replication

Fingerprint

Dive into the research topics of 'The Ebola virus VP35 protein is a suppressor of RNA silencing'. Together they form a unique fingerprint.

Cite this