A Retrovirus Stiffness Switch

逆转录病毒硬度开关

• 批准号: 7360356
• 负责人: Michael S Kay
• 金额: $ 22.04万
• 依托单位: UNIVERSITY OF UTAH
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-01 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7360356
• 关键词: Atomic Force Microscopy; Biochemical; Biological Process; Cells; Complex; Cytoplasmic Tail; Data; Electron Microscopy; Employee Strikes; HIV; Infection; Life Cycle Stages; Link; Measurement; Measures; Mechanics; Mediating; Methods; Peptide Hydrolases; Process; Property; Regulation; Reporting; Retroviridae; Role; Structure; Surface; Viral; Viral Envelope Proteins; Viral Fusion Proteins; Virion; Virus; Virus-like particle; complex biological systems; novel; particle; research study; tool

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.

描述（由申请人提供）：从细胞中出芽后，逆转录病毒（例如 HIV）会经历一个复杂的自发过程，称为成熟，这是其感染性所必需的。在成熟过程中，逆转录病毒会经历剧烈的内部重组。已通过生化和电子显微镜方法对 HIV 中的这些变化进行了广泛的表征。 最近，原子力显微镜（AFM）测量揭示了成熟过程中病毒体硬度的急剧下降（“硬度转换”）。有趣的是，这种硬度转换很大程度上是由病毒包膜（Env）蛋白控制的，该蛋白还介导病毒颗粒进入靶细胞的能力。拟议的研究将剖析 HIV 硬度开关的机制，并确定 Env 如何调节这种开关。目前的数据表明病毒体硬度和进入活性之间存在相关性。拟议的研究还将确定病毒机械特性是否直接控制病毒进入活动。这种新颖的调节机制将揭示逆转录病毒生命周期中以前未被认识到的复杂性，并将对其他复杂生物系统的机械调节产生更广泛的影响。