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Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture

Influenza A virus is a significant public health threat, but little is understood about the viral RNA structure and function. Current vaccines and therapeutic options to control influenza A virus infections are mostly protein-centric and of limited effectiveness. Here, we report using an ensemble de...

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Autores principales: Jiang, Tian, Nogales, Aitor, Baker, Steven F, Martinez-Sobrido, Luis, Turner, Douglas H
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896458/
https://www.ncbi.nlm.nih.gov/pubmed/27272307
http://dx.doi.org/10.1371/journal.pone.0156906
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author Jiang, Tian
Nogales, Aitor
Baker, Steven F
Martinez-Sobrido, Luis
Turner, Douglas H
author_facet Jiang, Tian
Nogales, Aitor
Baker, Steven F
Martinez-Sobrido, Luis
Turner, Douglas H
author_sort Jiang, Tian
collection PubMed
description Influenza A virus is a significant public health threat, but little is understood about the viral RNA structure and function. Current vaccines and therapeutic options to control influenza A virus infections are mostly protein-centric and of limited effectiveness. Here, we report using an ensemble defect approach to design mutations to misfold regions of conserved mRNA structures in influenza A virus segments 7 and 8. Influenza A mutant viruses inhibit pre-mRNA splicing and attenuate viral replication in cell culture, thus providing evidence for functions of the targeted regions. Targeting these influenza A viral RNA regions provides new possibilities for designing vaccines and therapeutics against this important human respiratory pathogen. The results also demonstrate that the ensemble defect approach is an efficient way to test for function of RNA sequences.
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spelling pubmed-48964582016-06-16 Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture Jiang, Tian Nogales, Aitor Baker, Steven F Martinez-Sobrido, Luis Turner, Douglas H PLoS One Research Article Influenza A virus is a significant public health threat, but little is understood about the viral RNA structure and function. Current vaccines and therapeutic options to control influenza A virus infections are mostly protein-centric and of limited effectiveness. Here, we report using an ensemble defect approach to design mutations to misfold regions of conserved mRNA structures in influenza A virus segments 7 and 8. Influenza A mutant viruses inhibit pre-mRNA splicing and attenuate viral replication in cell culture, thus providing evidence for functions of the targeted regions. Targeting these influenza A viral RNA regions provides new possibilities for designing vaccines and therapeutics against this important human respiratory pathogen. The results also demonstrate that the ensemble defect approach is an efficient way to test for function of RNA sequences. Public Library of Science 2016-06-07 /pmc/articles/PMC4896458/ /pubmed/27272307 http://dx.doi.org/10.1371/journal.pone.0156906 Text en © 2016 Jiang et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Jiang, Tian
Nogales, Aitor
Baker, Steven F
Martinez-Sobrido, Luis
Turner, Douglas H
Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture
title Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture
title_full Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture
title_fullStr Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture
title_full_unstemmed Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture
title_short Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture
title_sort mutations designed by ensemble defect to misfold conserved rna structures of influenza a segments 7 and 8 affect splicing and attenuate viral replication in cell culture
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4896458/
https://www.ncbi.nlm.nih.gov/pubmed/27272307
http://dx.doi.org/10.1371/journal.pone.0156906
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