Noncoding flavivirus RNA displays RNA interference suppressoractivity in insect and mammalian cells

Schnettler, Esther, Sterken, Mark G., Leung, Jason Y., Metz, Stefan W., Geertsema, Corinne, Goldbach, Rob W., Vlak, Just M., Kohl, Alain, Khromykh, Alexander A. and Pijlman, Gorben P. (2012) Noncoding flavivirus RNA displays RNA interference suppressoractivity in insect and mammalian cells. Journal of Virology, 86 24: 13486-13500. doi:10.1128/JVI.01104-12

Author Schnettler, Esther
Sterken, Mark G.
Leung, Jason Y.
Metz, Stefan W.
Geertsema, Corinne
Goldbach, Rob W.
Vlak, Just M.
Kohl, Alain
Khromykh, Alexander A.
Pijlman, Gorben P.
Title Noncoding flavivirus RNA displays RNA interference suppressoractivity in insect and mammalian cells
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
Publication date 2012-12
Year available 2012
Sub-type Article (original research)
DOI 10.1128/JVI.01104-12
Open Access Status DOI
Volume 86
Issue 24
Start page 13486
End page 13500
Total pages 15
Place of publication Washington, DC United States
Publisher American Society for Microbiology
Collection year 2013
Language eng
Formatted abstract
West Nile virus (WNV) and dengue virus (DENV) are highly pathogenic, mosquito-borne flaviviruses (family Flaviviridae) thatcause severe disease and death in humans. WNV and DENV actively replicate in mosquitoes and human hosts and thus encounterdifferent host immune responses. RNA interference (RNAi) is the predominant antiviral response against invading RNA virusesin insects and plants. As a countermeasure, plant and insect RNA viruses encode RNA silencing suppressor (RSS) proteinsto block the generation/activity of small interfering RNA (siRNA). Enhanced flavivirus replication in osquitoes depleted forRNAi factors suggests an important biological role for RNAi in restricting virus replication, but it has remained unclear whetheror not flaviviruses counteract RNAi via expression of an RSS. First, we established thaflaviviral RNA replication suppressedsiRNA-induced gene silencing in WNV and DENV replicon-expressing cells. Next, we showed that none of the WNV encodedproteins displayed RSS activity in mammalian and insect cells and in plants by using robust RNAi suppressor assays. In contrast,we found that the 3=-untranslated region-derived RNA molecule known as subgenomic flavivirus RNA (sfRNA) efficiently suppressedsiRNA-and miRNA-induced RNAi pathways in both mammalian and insect cells. We also showed that WNV sfRNA inhibitsin vitro cleavage of double-stranded RNA by Dicer. The results of the present study suggest a novel role for sfRNA, i.e., as anucleic acid-based regulator of RNAi pathways, a strategy that may be conserved among flaviviruses.
Keyword Animal Virus Replication
Antiviral Immunity
Arbovirus Infection
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
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