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

延伸因子 1 和基质在 HIV-1 核心分解中的作用

• 批准号: 7339913
• 负责人: David Richard Hout
• 金额: $ 4.68万
• 依托单位: VANDERBILT UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-07-10 至 2009-07-09
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7339913
• 关键词: Activated Lymphocyte; Address; Adverse effects; Affect; Amino Acids; Anti-Retroviral Agents; Antibodies; Area; Attenuated; Biological; Biological Assay; Biology; Capsid; Cell Line; Cells; Cytosol; Face; Fibrinogen; Gel; Genome; Goals; HIV; HIV-1; Highly Active Antiretroviral Therapy; Infection; Laboratories; Lead; Mass Spectrum Analysis; Mutate; Onset of illness; Patients; Peptide Elongation Factor 1; Play; Process; Proteins; RNA-Directed DNA Polymerase; Rate; Recombinants; Reporter; Research; Research Personnel; Role; Structure; T-Lymphocyte; Technology; Testing; Transportation; Viral; Viral Genome; Viral Load result; Viral Matrix Proteins; Virus; human EEF1A1 protein; interest; matrix protein, Human immunodeficiency virus type 1; mutant; novel; research study; size; stable cell line

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.

描述（由申请人提供）：HIV-1/艾滋病仍然是一个全球性的问题，因为没有治愈的存在。虽然有高度活性的抗逆转录病毒疗法可用于减少患者体内的病毒载量并延迟疾病的发作，但这些治疗费用昂贵，有许多副作用，并面临不断变异的病毒。最近，一些研究人员关注细胞因子在HIV-1复制的特定步骤中的作用，以开发抗逆转录病毒治疗的新靶点。其中一个新的研究领域集中在被误解的HIV-1核心脱壳过程。脱壳被具体定义为病毒锥形核心的分解和随后病毒基因组的释放。Aiken实验室已经确定HIV-1核心拆解是一个高度敏感的过程，对衣壳稳定性的微小改变敏感。核心稳定性的这些改变并没有破坏锥形结构，但损害了逆转录酶活性并减弱了HIV-1的复制。本研究的目的是确定在核心拆卸中发挥作用的病毒和细胞因子，以更好地了解HIV-1生物学。这一目标将通过实现三个具体目标来实现：1.鉴定在HIV-1核心分解中起作用的细胞因子。2.目的探讨该因子在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应开辟一个新的研究领域，进入艾滋病毒-1复制的早期后步骤，有可能确定新的抗逆转录病毒治疗的目标。