A Retrovirus Stiffness Switch

描述(申请人提供)：逆转录病毒(如HIV)从细胞中萌发后，经历一个复杂的自发过程，称为成熟，这是其传染性所必需的。在成熟过程中，逆转录病毒经历了戏剧性的内部重组。通过生化和电子显微镜方法，这些变化在HIV中得到了广泛的表征。 最近，原子力显微镜(AFM)的测量显示，病毒粒子在成熟过程中刚性急剧下降(“刚性开关”)。有趣的是，这种僵硬开关在很大程度上是由病毒包膜(Env)蛋白控制的，它也介导了病毒粒子进入靶细胞的能力。拟议的研究将剖析HIV僵硬开关的机制，并确定Env如何调节这一开关。目前的数据表明，病毒粒子硬度和进入活动之间存在相关性。拟议的研究还将确定病毒的机械特性是否直接控制病毒的进入活动。这种新的调控机制将揭示逆转录病毒生命周期中以前未被认识到的一层复杂性，并将对其他复杂生物系统的机械调控产生更广泛的影响。

DESCRIPTION (provided by applicant): After budding from the cell, retroviruses (such as HIV) undergo a complex spontaneous process called maturation that is required for their infectivity. During maturation retroviruses undergo dramatic internal reorganization. These changes have been extensively characterized in HIV by biochemical and electron microscopy methods. Very recently, atomic force microscopy (AFM) measurements have revealed a dramatic decrease in virion stiffness during maturation ("stiffness switch"). Interestingly, this stiffness switch is largely controlled by the viral envelope (Env) protein, which also mediates the ability of virions to enter target cells. The proposed studies will dissect the mechanism of the HIV stiffness switch and determine how Env regulates this switch. Current data suggests a correlation between virion stiffness and entry activity. The proposed studies will also determine if viral mechanical properties directly control viral entry activity. Such a novel regulatory mechanism would reveal a previously unappreciated layer of complexity in the retrovirus life-cycle and will have broader implications for mechanical regulation of other complex biological systems.