Investigating the Role of Innate Immune Factors in Restricting HIV Spread in Macrophages

研究先天免疫因子在限制 HIV 在巨噬细胞中传播中的作用

• 批准号: 9141343
• 负责人: David Jay Lubow
• 金额: $ 3.45万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-04-01 至 2017-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9141343
• 关键词: Ammonium Chloride; Anti-Retroviral Agents; Antiviral Agents; Binding; Binding Proteins; C-Type Lectins; Cell Culture Techniques; Cells; Complex; Cytoplasmic Tail; Data; Defect; Extracellular Domain; Goals; HIV; HIV Envelope Protein gp120; HIV Infections; HIV-1; Hela Cells; Immune; Immune Targeting; Immune system; In Vitro; Infection; Integration Host Factors; Interferon Type I; Interferon-alpha; Interferons; Investigation; Life; Lysosomes; Mediating; Modeling; Molecular; Natural Immunity; Outcome; Pharmaceutical Preparations; Phenotype; Production; Proteins; Publications; Research; Role; Subfamily lentivirinae; Testing; Viral; Viral Proteins; Virion; Virus; Work; cell type; global health; heterokaryon; innate immune function; insight; macrophage; mannose receptor; monocyte; mutant; novel; nuclease; pandemic disease; pressure; prevent; public health relevance; research and development; small hairpin RNA; transmission process; vector; viral DNA; vpr Gene Products

 DESCRIPTION (provided by applicant): The HIV--‐1 protein Vpr is highly conserved across all known lentiviruses, yet HIV mutants lacking vpr are capable of replicating in most cell culture models with little or no defect. The contrast between the evolutionary pressure to maintain indicate that in cultures of monocyte--‐derived macrophages a vpr--‐ vpr and its relative inconsequence in vitro has not been fully explained. Our earlier findings null mutant displays restricted virion production and Env expression. Additionally C--‐ type lectin expressed in macrophages that is known to bind the Env subunit our preliminary data suggest this restriction is dependent on mannose receptor, a gp120. Our proposed studies aim to determine how Env and virions are targeted and to confirm the identity of the restriction factor responsible for the defects we have observed. Successful completion of the project will provide insight into innate immunity and viral mechanisms of evasion.

 描述（由申请人提供）：HIV--1 蛋白 Vpr 在所有已知的慢病毒中高度保守，但缺乏 vpr 的 HIV 突变体能够在大多数细胞培养物中复制 几乎没有缺陷的模型。维持进化压力之间的对比表明，在单核细胞衍生的巨噬细胞培养物中，vpr-vpr及其在体外的相对不合理性尚未得到充分解释。我们早期的发现无效突变体显示病毒体产生和 Env 表达受到限制。此外，巨噬细胞中表达的 C 型凝集素已知与 Env 亚基结合，我们的初步数据表明这种限制取决于甘露糖受体（gp120）。我们提出的研究旨在确定 Env 和病毒体的靶向方式，并确认导致我们观察到的缺陷的限制因子的身份。该项目的成功完成将提供对先天免疫和病毒逃避机制的深入了解。