Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition
- Sara Cherry1,4,
- Tammy Doukas2,
- Susan Armknecht1,
- Sean Whelan3,
- Hui Wang1,
- Peter Sarnow2, and
- Norbert Perrimon1
- 1Harvard Medical School and Howard Hughes Medical Instutite, Department of Genetics, Boston Massachusetts 02115, USA; 2Stanford University School of Medicine, Department of Microbiology and Immunology, Stanford, California 94305, USA; 3Harvard Medical School, Department of Microbiology and Molecular Genetics, Boston Massachusetts 02115, USA
Abstract
The widespread class of RNA viruses that utilize internal ribosome entry sites (IRESs) for translation include poliovirus and Hepatitis C virus. To identify host factors required for IRES-dependent translation and viral replication, we performed a genome-wide RNAi screen in Drosophila cells infected with Drosophila C virus (DCV). We identified 66 ribosomal proteins that, when depleted, specifically inhibit DCV growth, but not a non-IRES-containing RNA virus. Moreover, treatment of flies with a translation inhibitor is protective in vivo. Finally, this increased sensitivity to ribosome levels also holds true for poliovirus infection of human cells, demonstrating the generality of these findings.
Keywords
Footnotes
-
Supplemental material is available at http://www.genesdev.org.
-
Article and publication are at http://www.genesdev.org/cgi/doi/10.1101/gad.1267905.
-
↵4 Corresponding author.
↵4 E-MAIL scherry{at}genetics.med.harvard.edu; FAX (617) 432-7688.
-
- Accepted December 16, 2004.
- Received September 30, 2004.
- Cold Spring Harbor Laboratory Press
