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.
- 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
- Received: October 22, 2020
- Accepted: January 11, 2021
- Accepted Manuscript published: January 12, 2021 (version 1)
© 2021, Mattenberger et al.
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