A tradeoff between enterovirus A71 particle stability and cell entry

Adam Catching, Ming Yeh, Simone Bianco, Sara Capponi () and Raul Andino ()
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Adam Catching: University of California in San Francisco
Ming Yeh: University of California in San Francisco
Simone Bianco: IBM Almaden Research Center
Sara Capponi: IBM Almaden Research Center
Raul Andino: University of California in San Francisco

Nature Communications, 2023, vol. 14, issue 1, 1-16

Abstract: Abstract A central role of viral capsids is to protect the viral genome from the harsh extracellular environment while facilitating initiation of infection when the virus encounters a target cell. Viruses are thought to have evolved an optimal equilibrium between particle stability and efficiency of cell entry. In this study, we genetically perturb this equilibrium in a non-enveloped virus, enterovirus A71 to determine its structural basis. We isolate a single-point mutation variant with increased particle thermotolerance and decreased efficiency of cell entry. Using cryo-electron microscopy and molecular dynamics simulations, we determine that the thermostable native particles have acquired an expanded conformation that results in a significant increase in protein dynamics. Examining the intermediate states of the thermostable variant reveals a potential pathway for uncoating. We propose a sequential release of the lipid pocket factor, followed by internal VP4 and ultimately the viral RNA.

Date: 2023
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DOI: 10.1038/s41467-023-43029-0

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