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dc.contributor.authorBailly, B
dc.contributor.authorRichard, C-A
dc.contributor.authorSharma, G
dc.contributor.authorWang, L
dc.contributor.authorJohansen, L
dc.contributor.authorCao, J
dc.contributor.authorPendharkar, V
dc.contributor.authorSharma, D-C
dc.contributor.authorGalloux, M
dc.contributor.authorWang, Y
dc.contributor.authorCui, R
dc.contributor.authorZou, G
dc.contributor.authorGuillon, P
dc.contributor.authorvon Itzstein, M
dc.contributor.authorEleouet, J-F
dc.contributor.authorAltmeyer, R
dc.date.accessioned2018-01-18T04:30:44Z
dc.date.available2018-01-18T04:30:44Z
dc.date.issued2016
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/srep25806
dc.identifier.urihttp://hdl.handle.net/10072/100673
dc.description.abstractHuman respiratory syncytial virus (hRSV) is a leading cause of acute lower respiratory tract infection in infants, elderly and immunocompromised individuals. To date, no specific antiviral drug is available to treat or prevent this disease. Here, we report that the Smoothened receptor (Smo) antagonist cyclopamine acts as a potent and selective inhibitor of in vitro and in vivo hRSV replication. Cyclopamine inhibits hRSV through a novel, Smo-independent mechanism. It specifically impairs the function of the hRSV RNA-dependent RNA polymerase complex notably by reducing expression levels of the viral antitermination factor M2-1. The relevance of these findings is corroborated by the demonstration that a single R151K mutation in M2-1 is sufficient to confer virus resistance to cyclopamine in vitro and that cyclopamine is able to reduce virus titers in a mouse model of hRSV infection. The results of our study open a novel avenue for the development of future therapies against hRSV infection.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Macmillan
dc.relation.ispartofpagefrom25806-1
dc.relation.ispartofpageto25806-11
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume6
dc.subject.fieldofresearchBiochemistry and Cell Biology not elsewhere classified
dc.subject.fieldofresearchcode060199
dc.titleTargeting human respiratory syncytial virus transcription anti-termination factor M2-1 to inhibit in vivo viral replication
dc.typeJournal article
dc.type.descriptionC1 - Articles
dc.type.codeC - Journal Articles
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.description.versionVersion of Record (VoR)
gro.facultyOffice of the Snr Dep Vice Chancellor, Institute for Glycomics
gro.rights.copyright© The Author(s). 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
gro.hasfulltextFull Text
gro.griffith.authorvon Itzstein, Mark
gro.griffith.authorAltmeyer, Ralf M.
gro.griffith.authorGuillon, Patrice M.
gro.griffith.authorBailly, Benjamin


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