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Globally defining the effects of mutations in a picornavirus capsid

The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. Despite their importance, a comprehensive understanding of how mutations affect viral fitness across different structural and functional attributes...

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Autores principales: Mattenberger, Florian, Latorre, Victor, Tirosh, Omer, Stern, Adi, Geller, Ron
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861617/
https://www.ncbi.nlm.nih.gov/pubmed/33432927
http://dx.doi.org/10.7554/eLife.64256
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author Mattenberger, Florian
Latorre, Victor
Tirosh, Omer
Stern, Adi
Geller, Ron
author_facet Mattenberger, Florian
Latorre, Victor
Tirosh, Omer
Stern, Adi
Geller, Ron
author_sort Mattenberger, Florian
collection PubMed
description The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. Despite their importance, a comprehensive understanding of how mutations affect viral fitness across different structural and functional attributes of the capsid is lacking. To address this limitation, we globally define the effects of mutations across the capsid of a human picornavirus. Using this resource, we identify structural and sequence determinants that accurately predict mutational fitness effects, refine evolutionary analyses, and define the sequence specificity of key capsid-encoded motifs. Furthermore, capitalizing on the derived sequence requirements for capsid-encoded protease cleavage sites, we implement a bioinformatic approach for identifying novel host proteins targeted by viral proteases. Our findings represent the most comprehensive investigation of mutational fitness effects in a picornavirus capsid to date and illuminate important aspects of viral biology, evolution, and host interactions.
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spelling pubmed-78616172021-02-08 Globally defining the effects of mutations in a picornavirus capsid Mattenberger, Florian Latorre, Victor Tirosh, Omer Stern, Adi Geller, Ron eLife Evolutionary Biology The capsids of non-enveloped viruses are highly multimeric and multifunctional protein assemblies that play key roles in viral biology and pathogenesis. Despite their importance, a comprehensive understanding of how mutations affect viral fitness across different structural and functional attributes of the capsid is lacking. To address this limitation, we globally define the effects of mutations across the capsid of a human picornavirus. Using this resource, we identify structural and sequence determinants that accurately predict mutational fitness effects, refine evolutionary analyses, and define the sequence specificity of key capsid-encoded motifs. Furthermore, capitalizing on the derived sequence requirements for capsid-encoded protease cleavage sites, we implement a bioinformatic approach for identifying novel host proteins targeted by viral proteases. Our findings represent the most comprehensive investigation of mutational fitness effects in a picornavirus capsid to date and illuminate important aspects of viral biology, evolution, and host interactions. eLife Sciences Publications, Ltd 2021-01-12 /pmc/articles/PMC7861617/ /pubmed/33432927 http://dx.doi.org/10.7554/eLife.64256 Text en © 2021, Mattenberger et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Evolutionary Biology
Mattenberger, Florian
Latorre, Victor
Tirosh, Omer
Stern, Adi
Geller, Ron
Globally defining the effects of mutations in a picornavirus capsid
title Globally defining the effects of mutations in a picornavirus capsid
title_full Globally defining the effects of mutations in a picornavirus capsid
title_fullStr Globally defining the effects of mutations in a picornavirus capsid
title_full_unstemmed Globally defining the effects of mutations in a picornavirus capsid
title_short Globally defining the effects of mutations in a picornavirus capsid
title_sort globally defining the effects of mutations in a picornavirus capsid
topic Evolutionary Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7861617/
https://www.ncbi.nlm.nih.gov/pubmed/33432927
http://dx.doi.org/10.7554/eLife.64256
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