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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...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2021
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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. |
format | Online Article Text |
id | pubmed-7861617 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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