Genome-wide RNAi screen reveals a specific sensitivity of IRES-containing RNA viruses to host translation inhibition.
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.
Cherry
Sara
S
Department of Genetics, Harvard Medical School and Howard Hughes Medical Instutite, Boston, Massachusetts 02115, USA. scherry@genetics.med.harvard.edu
Doukas
Tammy
T
Armknecht
Susan
S
Whelan
Sean
S
Wang
Hui
H
Sarnow
Peter
P
Perrimon
Norbert
N
D000818:Animals; D001483:Base Sequence; D017931:DNA Primers; D004330:Drosophila; D016679:Genome, Viral; D006367:HeLa Cells; D006801:Humans; D014176:Protein Biosynthesis; D034622:RNA Interference; D012328:RNA Viruses / Q000235:genetics* / Q000502:physiology; D014779:Virus Replication
D017931:DNA Primers