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.
Sequencing data have been uploaded to SRA (Bioproject PRJNA643896, SRA SRP269871, Accession SRX8663374-SRX8663384). All data used in the paper are either included as supplemental data and/or can be found at https://github.com/RGellerLab/CVB3_Capsid_DMS.
Deep mutational scanning of the CVB3 capsid proteinNCBI Bioproject, PRJNA643896.
- Ron Geller
- Ron Geller
- Florian Mattenberger
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
- Jan E Carette, Stanford University School of Medicine, United States
© 2021, Mattenberger et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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