Architecture and dynamics of immature HIV lattice

项目总结： 我们的长期目标是对调节组装、释放、 以及传染性艾滋病毒病毒粒子的成熟。新释放的HIV病毒粒子是未成熟的，具有蛋白质晶格 (主要是GAG多蛋白)，支撑他们的病毒膜。通过蛋白质分解，艾滋病毒酶有助于 把这个格子变成一个圆锥形的成熟核心，之后病毒就会传染。成熟抑制药， 一类新的抗病毒药物被设计成与未成熟的晶格结合并干扰这种转化。 在之前的获奖期间，我们证明了未成熟晶格的稳定性依赖于其他HIV 除了Gag多聚蛋白以外的其他成分。HIV病毒粒子的小尺寸使得对其晶格动力学的研究 因此，具有挑战性的是，我们开发了生物物理、成像和计算方法来实现这些 测量。我们在这个颁奖期有两个主要目标。我们的首要目标是调查具体的影响。 不同非GAG组分对未成熟晶格稳定性的影响并决定生物分子的性质 使其稳定的力量。我们的第二个目标是确定晶格内的动态如何驱动HIV的激活 酶和启动成熟的过程。通过提高我们对生物力学原理的理解 控制艾滋病毒的不成熟晶格及其成熟，我们的研究将为下一个- 新一代抗病毒药物以及未来的慢病毒系统。

Project Summary: Our long-term goal is to gain a molecular understanding of the machinery that regulates the assembly, release, and maturation of infectious HIV virions. Newly released HIV virions are immature and have a lattice of proteins (mainly the Gag polyprotein) that underpins their viral membrane. Through proteolysis, HIV enzymes help transform this lattice into a conical mature core, after which the virus becomes infectious. Maturation Inhibitors, a new class of antiviral drugs, are designed to bind to the immature lattice and interfere with this transformation. During the previous award period, we showed that the stability of the immature lattice is dependent on other HIV components aside from the Gag polyprotein. The small size of HIV virions makes studying their lattice dynamics challenging, therefore, we developed biophysical, imaging, and computational methods to enable these measurements. We have two main aims for this award period. Our first aim is to investigate the specific effects of different non-Gag components on the stability of the immature lattice and determine the nature of biomolecular forces stabilizing it. Our second aim is to determine how dynamics within the lattice drive the activation of HIV enzymes and kick start the maturation process. By advancing our understanding of the biomechanical principles governing the immature lattice of HIV and its maturation, our studies will inform both the design of next- generation antivirals as well as future lentiviral systems.