Long-Range Cooperative Disassembly and Aging During Adenovirus Uncoating

Icosahedral virus capsids are closed shells built up with a hexagonal lattice of proteins, which incorporate pentamers at their fivefold vertices. Human adenovirus particles lose pentamers (pentons) during infection under a variety of physicochemical cues, including mechanical pulling of molecular m...

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Autores principales: Natalia Martín-González, Pablo Ibáñez-Freire, Álvaro Ortega-Esteban, Mara Laguna-Castro, Carmen San Martín, Alejandro Valbuena, Rafael Delgado-Buscalioni, Pedro J. de Pablo
Formato: article
Lenguaje:EN
Publicado: American Physical Society 2021
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Acceso en línea:https://doaj.org/article/0450304d917a4b97b8719ae17be46390
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Sumario:Icosahedral virus capsids are closed shells built up with a hexagonal lattice of proteins, which incorporate pentamers at their fivefold vertices. Human adenovirus particles lose pentamers (pentons) during infection under a variety of physicochemical cues, including mechanical pulling of molecular motors and the viscous drag of the cytoplasm. By combining atomic force microscopy experiments with survival analysis and Markovian transition state theory, we investigate the sequence of adenovirus penton disassembly that reveals the aging of the virus structure. We show evidence that the lifetime of pentons gradually decreases, accompanied by capsid softening as neighboring pentons are lost. This cooperative dismantling process, which involves first-neighbor penton-penton distances of at least 45 nm, leads to a 50% increase in the virus disassembling rate of the virus particle. Theory and experiments fit remarkably well, allowing us to obtain the spontaneous escape rate and the energy barrier of penton disassembly (∼30 k_{B}T). The observed increase in the penton’s loss rate reveals long-range structural correlations within the capsid. Our estimations suggest that the mechanical cues arising from the strokes of protein motors carrying the virus to the nucleus could help penton disassembly and warrant the timely delivery of weak-enough capsids for adenovirus infection.