Kra Kalouna, Li Siyu, Gargowitsch Laetitia, Degrouard Jéril, Pérez Javier, Zandi Roya, Bressanelli Stéphane, Tresset Guillaume
Université Paris-Saclay, CNRS, Laboratoire de Physique des Solides, 91405 Orsay, France.
Université Paris-Saclay, CEA, CNRS, Institute for Integrative Biology of the Cell (I2BC), 91198 Gif-sur-Yvette, France.
ACS Nano. 2023 Jul 11;17(13):12723-12733. doi: 10.1021/acsnano.3c03595. Epub 2023 Jun 21.
Capsid assembly modulators (CAMs) are antiviral molecules that disturb the formation of icosahedral viral capsids, in particular, those of the Hepatitis B virus (HBV). We report an integrated, physics-driven study elucidating quantitatively the effects of two classes of CAMs on the HBV capsid assembly. Time-resolved small-angle X-ray scattering measurements revealed accelerated self-assembly processes that implied the increase of subunit binding energy from 9- up to 18-fold the thermal energy due to CAMs. Cryotransmission electron microscopy images showed that both classes induce various changes in capsid morphology: from a slight elongation, unrecognized in previous work, to a strong deformation with a capsid size more than twice as large. The observed capsid morphologies were closely reproduced in coarse-grained simulations by varying the Föppl-von-Kármán number, thus pointing out the role of CAMs in altering the capsid elastic energy. Our results illuminate the mechanisms of action of CAMs on HBV capsid assembly at high spatiotemporal resolution and may bring perspectives on virus-derived nanocapsules with tunable morphologies.
衣壳组装调节剂（CAMs）是一类抗病毒分子，可干扰二十面体病毒衣壳的形成，尤其是乙型肝炎病毒（HBV）衣壳。我们报告了一项综合的、基于物理学的研究，定量阐明了两类CAMs对HBV衣壳组装的影响。时间分辨小角X射线散射测量揭示了加速的自组装过程，这意味着由于CAMs的作用，亚基结合能增加到热能的9至18倍。低温透射电子显微镜图像显示，这两类调节剂都会引起衣壳形态的各种变化：从之前研究中未识别出的轻微伸长，到衣壳尺寸增大两倍多的强烈变形。通过改变弗普尔-冯·卡门数，在粗粒度模拟中密切再现了观察到的衣壳形态，从而指出了CAMs在改变衣壳弹性能方面的作用。我们的结果在高时空分辨率下阐明了CAMs对HBV衣壳组装的作用机制，并可能为具有可调形态的病毒衍生纳米胶囊带来新的前景。
