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Long-Range Cooperative Disassembly and Aging During Adenovirus Uncoating
Physical Review X ( IF 12.5 ) Pub Date : 2021-04-30 , DOI: 10.1103/physrevx.11.021025
Natalia Martín-González , Pablo Ibáñez-Freire , Álvaro Ortega-Esteban , Mara Laguna-Castro , Carmen San Martín , Alejandro Valbuena , Rafael Delgado-Buscalioni , Pedro J. de Pablo

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 (30kBT). 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.

中文翻译:

腺病毒脱壳过程中的远程合作拆卸和老化

二十面体病毒衣壳是封闭的壳,由六边形的蛋白质网格构成,该蛋白质的五倍顶点处带有五聚体。在感染过程中,人类腺病毒颗粒会在多种物理化学提示下失去五聚体(戊烯),包括分子马达的机械拉动和细胞质的粘性阻力。通过将原子力显微镜实验与生存分析和马尔可夫过渡态理论相结合,我们研究了腺病毒五聚体分解的序列,揭示了病毒结构的老化。我们显示的证据表明,戊烯的寿命逐渐减少,伴随着衣壳的软化,因为邻近的戊烯丢失了。这种协作拆卸过程涉及至少45 nm的第一邻居戊烯-戊酮距离,导致病毒颗粒的病毒分解率提高50%。理论和实验非常吻合,使我们能够获得自发逃逸率和戊烯分解的能垒(30ķŤ)。观察到的戊烯损失率的增加揭示了衣壳内的长期结构相关性。我们的估计表明,将病毒携带到核中的蛋白质运动的冲程所产生的机械提示可能有助于戊烯的拆卸,并保证及时递送足够弱的衣壳用于腺病毒感染。
更新日期:2021-04-30
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