Quantitative Single-Cell Assessment of Lentivirus Susceptibility Determinants

慢病毒敏感性决定因素的定量单细胞评估

• 批准号: 10486970
• 负责人: Alex Compton
• 金额: $ 21.62万
• 依托单位: DIVISION OF BASIC SCIENCES - NCI
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10486970
• 关键词: Address; Affect; Antiviral Agents; Biology; Biosensor; Cell fusion; Cells; Cholesterol; Collaborations; Complex; Coupling; Flow Cytometry; Foundations; Gene Expression; Gene Expression Profile; Gene Proteins; Genes; HIV; HIV Infections; HIV-1; Heterogeneity; Human; Immunity; Interferons; Lentivirus; Lentivirus Infections; Life Cycle Stages; Lipids; Membrane Fluidity; Metabolic; Methods; Microscopy; Molecular Conformation; Plasmids; Population; Predisposition; Process; Production; Proteins; Publications; Resistance to infection; Resolution; Robotics; Technology; Tissues; Transcript; Universities; Viral Fusion Proteins; Virion; Virus; Virus Diseases; Work; differential expression; next generation sequencing

Following our initial publication in which we identified that cholesterol levels induced by glycolytic activity are critical for efficient HIV-1 fusion with humans cells (Coomer et al., PLoS Pathog. 16: e1008359, 2020), we are employing some of the same experimental methods to better understand the impact that host cell lipids and host antiviral proteins have on HIV fusion with target cells. Specifically, we are addressing how HIV virion content affects the function of HIV Envelope, the viral fusion protein responsible for gaining entry into cells. We aim to understand how the conformational dynamics and clustering of Envelope are impacted by interferon and interferon-stimulated genes that regulate membrane fluidity of the HIV virion. This work is in progress and ongoing.

在我们最初发表的论文中，我们确定了糖酵解活动引起的胆固醇水平对于HIV-1与人类细胞的有效融合是至关重要的(Comer等人，PLoS pathog。16：E1008359,2020)，我们正在采用一些相同的实验方法，以更好地了解宿主细胞脂类和宿主抗病毒蛋白对HIV与目标细胞融合的影响。具体地说，我们正在研究HIV病毒粒子的含量如何影响HIV包膜的功能，HIV包膜是负责进入细胞的病毒融合蛋白。我们的目标是了解干扰素和干扰素刺激的基因如何影响包膜的构象动力学和聚集性，这些基因调节HIV病毒粒子的膜流动性。这项工作正在进行中，正在进行中。