Genomic RNA folding mediates assembly of human parechovirus

Shabih Shakeel; Eric C. Dykeman; Simon J. White; Ari Ora; Joseph J B Cockburn; Sarah J. Butcher; Peter G. Stockley; Reidun Twarock

doi:10.1038/s41467-016-0011-z

Genomic RNA folding mediates assembly of human parechovirus

Shabih Shakeel, Eric C. Dykeman, Simon J. White, Ari Ora, Joseph J B Cockburn, Sarah J. Butcher^*, Peter G. Stockley, Reidun Twarock

^*Corresponding author for this work

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Abstract

Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets.

Original language	English
Article number	5
Pages (from-to)	1-11
Number of pages	11
Journal	Nature Communications
Volume	8
Issue number	1
DOIs	https://doi.org/10.1038/s41467-016-0011-z
Publication status	Published - 1 Dec 2017
MoE publication type	A1 Journal article-refereed

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abstract = "Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets.",

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AU - Butcher, Sarah J.

AU - Stockley, Peter G.

AU - Twarock, Reidun

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AB - Assembly of the major viral pathogens of the Picornaviridae family is poorly understood. Human parechovirus 1 is an example of such viruses that contains 60 short regions of ordered RNA density making identical contacts with the protein shell. We show here via a combination of RNA-based systematic evolution of ligands by exponential enrichment, bioinformatics analysis and reverse genetics that these RNA segments are bound to the coat proteins in a sequence-specific manner. Disruption of either the RNA coat protein recognition motif or its contact amino acid residues is deleterious for viral assembly. The data are consistent with RNA packaging signals playing essential roles in virion assembly. Their binding sites on the coat proteins are evolutionarily conserved across the Parechovirus genus, suggesting that they represent potential broad-spectrum anti-viral targets.

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Genomic RNA folding mediates assembly of human parechovirus

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