Drifting Motions of the Adenovirus Receptor CAR and Immobile Integrins Initiate Virus Uncoating and Membrane Lytic Protein Exposure
Drifting Motions of the Adenovirus Receptor CAR and Immobile Integrins Initiate Virus Uncoating and Membrane Lytic Protein Exposure
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DOI：
10.1016/j.chom.2011.07.006
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发表时间：
2011-08-18
影响因子：
30.3
通讯作者：
Greber, Urs F.
中科院分区：
文献类型：
--
作者：
Burckhardt, Christoph J.;Suomalainen, Maarit;Greber, Urs F.
病毒颗粒与质膜受体结合，引起病毒运动，招募信号蛋白，触发膜弯曲和分裂，最终导致内吞病毒摄取。在这里，我们分析了人腺病毒如何与其受体柯萨奇病毒腺病毒受体(CAR)和辅助受体αv整合素在质膜上运动。病毒通过纤维结节与CAR结合，导致扩散运动和肌动球蛋白-2依赖的漂移，而整合素靶向病毒在空间上受到更多限制。随后内化的病毒颗粒可以特别观察到扩散、漂移和受限运动。CAR介导的漂移与整合素结合一起支持了腺病毒颗粒的纤维脱落，导致了膜裂解的内部病毒蛋白VI的暴露，并增强了病毒对内体的逃逸。我们的结果表明，腺病毒的脱膜是通过CAR漂移运动和与固定的整合素结合而在质膜上开始的。
Viral particle binding to plasma membrane receptors elicits virus motions, recruits signaling proteins, and triggers membrane bending and fission, finally resulting in endocytic virus uptake. Here we analyze how human adenovirus engages its receptor coxsackievirus adenovirus receptor (CAR) and coreceptor alpha v integrin to move on the plasma membrane. Virus binding to CAR through fiber knobs gave rise to diffusive motions and actomyosin-2-dependent drifts, while integrin-targeted viruses were spatially more confined. Diffusions, drifts, and confined motions were specifically observed with viral particles that were subsequently internalized. CAR-mediated drifts together with integrin binding supported fiber shedding from adenovirus particles, leading to exposure of the membrane-lytic internal virion protein VI and enhanced viral escape from endosomes. Our results show that adenovirus uncoating is initiated at the plasma membrane by CAR drifting motion and binding to immobile integrins.