Globally defining the effects of mutations in a picornavirus capsid

Florian Mattenberger, Victor Latorre, Omer Tirosh, Adi Stern, Ron Geller*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article numbere64256
Pages (from-to)1-56
Number of pages56
JournaleLife
Volume10
DOIs
StatePublished - Jan 2021

Funding

FundersFunder number
Ministerio de Ciencia, Innovación y Universidades
European Commission

    Keywords

    • Capsid
    • Deep mutational scanning
    • Mutational fitness effects
    • Picornavirus
    • Viral protease

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