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dc.contributor.authorGomila, Raúl C.
dc.contributor.authorMartin, Glover III
dc.contributor.authorGehrke, Lee
dc.date.accessioned2019-10-05T09:47:06Z
dc.date.issued2011
dc.identifier.citationGomila, Raúl C., Glover W. Martin, and Lee Gehrke. 2011. “NF90 Binds the Dengue Virus RNA 3′ Terminus and Is a Positive Regulator of Dengue Virus Replication.” Edited by Kylene Kehn-Hall. PLoS ONE 6 (2): e16687. https://doi.org/10.1371/journal.pone.0016687.
dc.identifier.issn1932-6203
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:41483186*
dc.description.abstractBackground: Viral RNA translation and replication are regulated by sequence and structural elements in the 5' and 3' untranslated regions (UTR) and by host cell and/or viral proteins that bind them. Dengue virus has a single-stranded RNA genome with positive polarity, a 5' m7GpppG cap, and a conserved 3'-terminal stem loop (SL) that is linked to proposed functions in viral RNA transcription and translation. Mechanisms explaining the contributions of host proteins to viral RNA translation and replication are poorly defined, yet understanding host protein-viral RNA interactions may identify new targets for therapeutic intervention. This study was directed at identifying functionally significant host proteins that bind the conserved dengue virus RNA 3' terminus.Methodology/Principal Findings: Proteins eluted from a dengue 3' SL RNA affinity column at increasing ionic strength included two with double-strand RNA binding motifs (NF90/DRBP76 and DEAH box polypeptide 9/RNA helicase A (RHA)), in addition to NF45, which forms a heterodimer with NF90. Although detectable NF90 and RHA proteins localized to the nucleus of uninfected cells, immunofluorescence revealed cytoplasmic NF90 in dengue virus-infected cells, leading us to hypothesize that NF90 has a functional role(s) in dengue infections. Cells depleted of NF90 were used to quantify viral RNA transcript levels and production of infectious dengue virus. NF90 depletion was accompanied by a 50%-70% decrease in dengue RNA levels and in production of infectious viral progeny. Conclusions: /Significance: The results indicate that NF90 interacts with the 3' SL structure of the dengue RNA and is a positive regulator of dengue virus replication. NF90 depletion diminished the production of infectious dengue virus by more than 50%, which may have important significance for identifying therapeutic targets to limit a virus that threatens more than a billion people worldwide.
dc.language.isoen_US
dc.publisherPublic Library of Science
dash.licenseLAA
dc.titleNF90 Binds the Dengue Virus RNA 3′ Terminus and Is a Positive Regulator of Dengue Virus Replication
dc.typeJournal Article
dc.description.versionVersion of Record
dc.relation.journalPloS One
dash.depositing.authorGehrke, Lee::9dd4debe525adf14dab8fe15f7ce64bd::600
dc.date.available2019-10-05T09:47:06Z
dash.workflow.comments1Science Serial ID 83526
dc.identifier.doi10.1371/journal.pone.0016687
dash.source.volume6;2


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