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dc.contributor.authorFros, Jelke J.
dc.contributor.authorDietrich, Isabelle
dc.contributor.authorAlshaikhahmed, Kinda
dc.contributor.authorPasschier, Tim C.
dc.contributor.authorEvans, David John
dc.contributor.authorSimmonds, Peter
dc.date.accessioned2017-10-27T15:30:07Z
dc.date.available2017-10-27T15:30:07Z
dc.date.issued2017-09-29
dc.identifier.citationFros , J J , Dietrich , I , Alshaikhahmed , K , Passchier , T C , Evans , D J & Simmonds , P 2017 , ' CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry ' , eLife , vol. 6 , e29112 . https://doi.org/10.7554/eLife.29112en
dc.identifier.issn2050-084X
dc.identifier.otherPURE: 251245103
dc.identifier.otherPURE UUID: 59389387-ad45-4b2c-9e0d-6be5999e36de
dc.identifier.otherScopus: 85032974482
dc.identifier.otherWOS: 000413821600001
dc.identifier.urihttp://hdl.handle.net/10023/11936
dc.descriptionFunding: Wellcome (WT103767MA) Peter Simmonds.en
dc.description.abstractMost vertebrate and plant RNA and small DNA viruses suppress genomic CpG and UpA dinucleotide frequencies, apparently mimicking host mRNA composition. Artificially increasing CpG/UpA dinucleotides attenuates viruses through an entirely unknown mechanism. Using the echovirus 7 (E7) model in several cell types, we show that the restriction in E7 replication in mutants with increased CpG/UpA dinucleotides occurred immediately after viral entry, with incoming virions failing to form replication complexes. Sequences of CpG/UpA-high virus stocks showed no evidence of increased mutational errors that would render them replication defective, these viral RNAs were not differentially sequestered in cytoplasmic stress granules nor did they induce a systemic antiviral state. Importantly, restriction was not mediated through effects on translation efficiency since replicons with high CpG/UpA sequences inserted into a non-coding region were similarly replication defective. Host-cells thus possess intrinsic defence pathways that prevent replication of viruses with increased CpG/UpA frequencies independently of codon usage.
dc.format.extent29
dc.language.isoeng
dc.relation.ispartofeLifeen
dc.rightsCopyright Fros et al 2017. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited.en
dc.subjectQR355 Virologyen
dc.subjectRC Internal medicineen
dc.subjectNDASen
dc.subject.lccQR355en
dc.subject.lccRCen
dc.titleCpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entryen
dc.typeJournal articleen
dc.description.versionPublisher PDFen
dc.contributor.institutionUniversity of St Andrews.School of Biologyen
dc.contributor.institutionUniversity of St Andrews.Biomedical Sciences Research Complexen
dc.identifier.doihttps://doi.org/10.7554/eLife.29112
dc.description.statusPeer revieweden


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