Defining the microtubule motors which drive the uncoating and trafficking of HIV

 描述（由申请人提供）： HIV-1脱壳是一个知之甚少的领域，加强这一机制背后的想法将为病毒的生命周期和抗病毒治疗的有趣靶点提供坚实的基础。我们以前的工作微管在HIV-1脱壳过程中的作用提供了有价值的信息，贩运和HIV-1脱壳领域。我们的初步工作支持一个强烈的依赖性的几个微管相关蛋白（MAP）在HIV-1的脱壳和参与各种其他宿主因素在这个过程中。有了这个，我们提出了三个具体的目标，探索这些地图在HIV-1脱壳的作用。我们的第一个目标是破译这些MAP控制病毒脱壳的机制。在第二个目标中，我们将进一步描述病毒核心运输是如何由这些MAP控制的，在最后一个目标中，我们将定义MAP和病毒核心之间的直接相互作用，这有助于HIV-1的脱壳和运输。我们的专业知识和合作将有助于实现这些具体目标，并显示微管运输机制如何在HIV-1脱壳过程中发挥重要作用。这些目标的发现将为推动HIV-1脱壳和贩运的分子相互作用提供重要的理解，并将有助于确定未来抗病毒治疗的更好候选者。

 DESCRIPTION (provided by applicant): HIV-1 uncoating is a poorly understood field and strengthening the idea behind this mechanism will add a strong base to the viral life cycle and interesting targets for antiviral therapy. Our previous work on the role of microtubules during HIV-1 uncoating has provided valuable information to the field of trafficking and HIV-1 uncoating. Our preliminary work supports a strong dependency of several microtubule associated proteins (MAPs) during HIV-1 uncoating and involvement of a variety of other host factors in this process. With this, we propose three specific aims to explore the role of these MAPs during HIV-1 uncoating. Our first aim would be to decipher a mechanism by which these MAPs control viral uncoating. In the second aim, we would further characterize how the viral core trafficking is controlled by these MAPs and in the last aim, we would define the direct interactions between MAPs and the viral core which contribute to HIV-1 uncoating and trafficking. Our expertise and collaborations would help achieve these specific aims and show how the microtubule trafficking machinery plays an important role during HIV-1 uncoating. Findings from these proposed aims will provide critical understanding to the molecular interactions which drive HIV-1 uncoating and trafficking and would help identify better candidates for future antiviral therapy.