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A tradeoff between enterovirus A71 particle stability and cell entry

Author

Listed:
  • Adam Catching

    (University of California in San Francisco
    University of California in San Francisco)

  • Ming Yeh

    (University of California in San Francisco)

  • Simone Bianco

    (IBM Almaden Research Center
    Center for Cellular Construction
    Altos Labs)

  • Sara Capponi

    (IBM Almaden Research Center
    Center for Cellular Construction)

  • Raul Andino

    (University of California in San Francisco)

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.

Suggested Citation

  • Adam Catching & Ming Yeh & Simone Bianco & Sara Capponi & Raul Andino, 2023. "A tradeoff between enterovirus A71 particle stability and cell entry," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-43029-0
    DOI: 10.1038/s41467-023-43029-0
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    References listed on IDEAS

    as
    1. Jacqueline Staring & Eleonore von Castelmur & Vincent A. Blomen & Lisa G. van den Hengel & Markus Brockmann & Jim Baggen & Hendrik Jan Thibaut & Joppe Nieuwenhuis & Hans Janssen & Frank J. M. van Kupp, 2017. "PLA2G16 represents a switch between entry and clearance of Picornaviridae," Nature, Nature, vol. 541(7637), pages 412-416, January.
    2. Marco Vignuzzi & Jeffrey K. Stone & Jamie J. Arnold & Craig E. Cameron & Raul Andino, 2006. "Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population," Nature, Nature, vol. 439(7074), pages 344-348, January.
    3. Ron Geller & Sebastian Pechmann & Ashley Acevedo & Raul Andino & Judith Frydman, 2018. "Hsp90 shapes protein and RNA evolution to balance trade-offs between protein stability and aggregation," Nature Communications, Nature, vol. 9(1), pages 1-11, December.
    Full references (including those not matched with items on IDEAS)

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