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bioRxiv · 10.1101/709824

Conformational Dynamics of Nonenveloped Circovirus Capsid to the Host Cell Receptor

Li, J.·Gu, J.·Wang, S.·Lin, C.·Zhou, J.·Lei, J.
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Abstract

Circovirus, comprising one capsid protein, is the smallest nonenveloped virus and induces lymphopenia. Circovirus can be used to explore the cell adhesion mechanism of nonenveloped viruses. We developed a single-molecule fluorescence resonance energy transfer (smFRET) assay to directly visualize the capsids conformational feature. The capsid underwent reversible dynamic transformation between three conformations. The cell surface receptor heparan sulfate (HS) altered the dynamic equilibrium of the capsid to the high-FRET state, revealing the HS binding region. Neutralizing antibodies restricted capsid transition to a low-FRET state, masking the HS binding domain. The lack of positively charged amino acids in the HS binding site reduced cell surface affinity and attenuated virus infectivity via conformational changes. These intrinsic characteristics of the capsid suggested that conformational dynamics is critical for the structural changes occurring upon cell surface receptor binding, supporting a dynamics-based mechanism of receptor binding.\n\nImportanceViral proteins were commom working as ligand to interacte with cell surface glycosaminoglycan receptors to achieve the virus attachment, during which the conformational dynamics of the protein ligand are also vital for the binding properties. In this study, PCV2 capsid and heparin sulfate were used to study the protein conformational dynamics of nonenveloped and icosahedral circovirus capsid during triggering to cell surface receptor. we demonstrated the PCV2 capsid could acts as a dynamic machine, spontaneously adopting multiple conformations with reversible interconversion and intrinsic conformational features could be regulated by glycosaminoglycan receptors and neutralizing antibodies. These increased our understanding of the mechanism by which nonenveloped virus attach to cells.

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Li, J., Gu, J., Wang, S., Lin, C., Zhou, J., Lei, J.. 2019-07-21. Conformational Dynamics of Nonenveloped Circovirus Capsid to the Host Cell Receptor. https://doi.org/10.1101/709824

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