The roles od Elongation Factor 1 and Matrix in HIV-1 core disassembly

描述(申请人提供)：艾滋病毒-1/艾滋病仍然是一个全球性问题，因为目前还没有治愈的方法。虽然可以使用高效的抗逆转录病毒疗法来减少患者的病毒载量并推迟疾病的发生，但这些治疗方法成本高昂，副作用众多，而且面临着不断变异的病毒。最近，一些研究人员关注细胞因子在HIV-1复制的特定步骤中所起的作用，以期为抗逆转录病毒治疗开发新的靶点。其中一个新的研究领域专注于被误解的HIV-1核心去涂层过程。去包被专门定义为病毒锥形核心的解体和随后病毒基因组的释放。艾肯实验室已经证实，HIV-1核心解体是一个高度敏感的过程，容易受到衣壳稳定性的微小变化的影响。核心稳定性的这些变化并没有破坏锥形结构，但削弱了逆转录酶的活性，并减弱了HIV-1的复制。这项研究的目的是确定在核心解体中发挥作用的病毒和细胞因子，以便更好地了解HIV-1生物学。这一目标将通过解决三个具体目标来实现：1.确定在HIV-1核心分解中起作用的细胞因子。2.确定该因子在HIV-1感染中的生物学意义。3.确定核心相关病毒MA在HIV-1脱壳中的作用，并确定MA中负责脱壳的特定残基。这三个具体目标的完成将为艾滋病毒-1复制的早期进入后步骤开辟一个新的研究领域，并有可能确定新的抗逆转录病毒治疗目标。

DESCRIPTION (provided by applicant): HIV-1/AIDS continues to be a global problem as no cure exists. While highly active anti-retroviral therapy is available to reduce viral loads in patients and delay the onset of disease, these treatments are costly, have numerous side effects and face a constantly mutating virus. Recently, some researchers have focused on the role cellular factors play on specific steps of HIV-1 replication in order to develop new targets for anti- retroviral therapy. One such new area of study focuses on the misunderstood process of HIV-1 core uncoating. Uncoating is defined specifically as the disassembly of the viral conical core and subsequent release of the viral genome. The Aiken laboratory has established that HIV-1 core disassembly is a highly sensitive process susceptible to small alterations in capsid stability. These alterations in core stability did not disrupt the conical structure but impaired reverse transcriptase activity and attenuated HIV-1 replication. The objective of this research is to identify the viral and cellular factors that play a role in core disassembly in order to achieve a better understanding of HIV-1 biology. This objective will be achieved by addressing three specific aims: 1. To identify a cellular factor that plays a role in HIV-1 core disassembly. 2. To determine the biological significance of this factor on HIV-1 infection. 3. To determine the role of core associated viral MA in HIV-1 uncoating and identify specific residues in MA responsible for uncoating. Completion of these three specific aims should open up a new area of research into the early post entry steps of HIV-1 replication with the possibility for identifying novel targets of anti-retroviral therapy.