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Published on: November 12, 2015
Monitoring dynamics of human adenovirus disassembly induced by mechanical fatigue
A Ortega-Esteban1, A J Pérez-Berná, R Menéndez-Conejero
1Departamento de Física de la Materia Condensada, Universidad Autónoma de Madrid, 28049 Madrid, Spain.
Abstract:
The standard pathway for virus infection of eukaryotic cells requires disassembly of the viral shell to facilitate release of the viral genome into the host cell. Here we use mechanical fatigue, well below rupture strength, to induce stepwise disruption of individual human adenovirus particles under physiological conditions, and simultaneously monitor disassembly in real time. Our data show the sequence of dismantling events in individual mature (infectious) and immature (noninfectious) virions, starting with consecutive release of vertex structures followed by capsid cracking and core exposure. Further, our experiments demonstrate that vertex resilience depends inextricably on maturation, and establish the relevance of penton vacancies as seeding loci for virus shell disruption. The mechanical fatigue disruption route recapitulates the adenovirus disassembly pathway in vivo, as well as the stability differences between mature and immature virions.
Insights
Mechanical fatigue disrupts human adenovirus particles, revealing stepwise disassembly. This process mimics in vivo virus infection and highlights how maturation affects viral shell stability and infection.
Area of Science:
- Virology
- Biophysics
- Structural Biology
Background:
- Viral infection necessitates viral shell disassembly for genome release into host cells.
- Understanding adenovirus disassembly is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the mechanical disruption of human adenovirus particles.
- To elucidate the real-time, stepwise disassembly process of mature and immature virions.
- To identify key factors influencing viral shell stability during disassembly.
Main Methods:
- Applying mechanical fatigue, below rupture strength, to individual human adenovirus particles under physiological conditions.
- Simultaneously monitoring viral particle disassembly in real time using advanced imaging techniques.
- Analyzing the sequence of dismantling events, including vertex structure release, capsid cracking, and core exposure.
Main Results:
- Demonstrated stepwise disruption of adenovirus particles initiated by vertex structure release.
- Observed differences in vertex resilience between mature (infectious) and immature (noninfectious) virions, with maturation increasing resilience.
- Identified penton vacancies as critical sites for initiating virus shell disruption.
Conclusions:
- Mechanical fatigue provides a novel route to study adenovirus disassembly, recapitulating in vivo pathways.
- Viral maturation significantly impacts capsid stability and disassembly dynamics.
- Penton vacancies play a crucial role in initiating the mechanical breakdown of the adenovirus shell.

