CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.

Most 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 c...

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Main Authors: Fros, JJ, Dietrich, I, Alshaikhahmed, K, Passchier, TC, Evans, DJ, Simmonds, P
Format: Journal article
Language:English
Published: eLife Sciences 2017
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author Fros, JJ
Dietrich, I
Alshaikhahmed, K
Passchier, TC
Evans, DJ
Simmonds, P
author_facet Fros, JJ
Dietrich, I
Alshaikhahmed, K
Passchier, TC
Evans, DJ
Simmonds, P
author_sort Fros, JJ
collection OXFORD
description Most 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.
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spelling oxford-uuid:fafdfc6f-2a42-4b22-8102-510f1e36bb912022-03-27T13:10:33ZCpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:fafdfc6f-2a42-4b22-8102-510f1e36bb91EnglishSymplectic Elements at OxfordeLife Sciences2017Fros, JJDietrich, IAlshaikhahmed, KPasschier, TCEvans, DJSimmonds, PMost 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.
spellingShingle Fros, JJ
Dietrich, I
Alshaikhahmed, K
Passchier, TC
Evans, DJ
Simmonds, P
CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.
title CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.
title_full CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.
title_fullStr CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.
title_full_unstemmed CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.
title_short CpG and UpA dinucleotides in both coding and non-coding regions of echovirus 7 inhibit replication initiation post-entry.
title_sort cpg and upa dinucleotides in both coding and non coding regions of echovirus 7 inhibit replication initiation post entry
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