HIV AND NF-KB INTERACTIONS IN MONOCYTES

HIV 和 NF-KB 在单核细胞中的相互作用

• 批准号: 2886919
• 负责人: CARLOS V PAYA
• 金额: $ 22.16万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 1994
• 资助国家: 美国
• 起止时间: 1994-08-01 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2886919
• 关键词: HIV infections; biological signal transduction; casein kinase; host organism interaction; human immunodeficiency virus; human tissue; immunoprecipitation; macrophage; monocyte; phosphorylation; protein structure function; second messengers; tissue /cell culture; transcription factor; virus infection mechanism; virus replication

DESCRIPTION (adapted from the proposal) Macrophages play a key role in the pathogenesis of HIV infection, in that they serve as a main reservoir of persistent viral replication throughout the infection. However, the mechanisms regulating viral persistence remain uncharacterized. The NF-kB/rel family of transcription factors is essential for HIV transcription and replication in macrophages. NF-kB activity is constitutive in the nuclei of macrophages, in the form of RelB, and exists as a cytosolic and inducible pool of NF-kB (p50/65) associated with IkB. Studies from this lab have identified components of NF-kB that are unique to macrophages, this includes the targeting of IkBa and nuclear translocation of NF-kB following HIV infection. This process is regulated by induced kinases that phosphorylate IkBa at S32/36. These workers have identified an inducible IkBa kinase in macrophages, casein kinase II (PK-CK2). The primary goal of the proposal is to characterize the molecular mechanisms whereby NF-kB participates in the regulation of HIV persistence in human macrophages. The aims are: 1) to characterize the molecular composition and regulation of constitutive NF-kB (RelB) activity and its relevance to virus replication; 2) to study the mechanisms of HIV-dependent activation of the induced pool of NF-kB through IkBa targeting; and 3) to characterize the function of the inducible IkBa kinase and the relationship to PK-CK2.

描述（改编自提案）宏观经济在 艾滋病毒感染的发病机制，因为它们作为一个主要的水库， 在整个感染过程中持续的病毒复制。 但 调节病毒持久性的机制仍然没有特征。 的 NF-kB/rel家族转录因子是HIV转录所必需的 和在巨噬细胞中的复制。 NF-kB活性是组成性的， 巨噬细胞的细胞核，以RelB的形式存在，并作为胞质和 与IkB相关的NF-kB（p50/65）的诱导池。 这个实验室的研究 已经确定了巨噬细胞特有的NF-κ B成分， 包括IkBa的靶向和NF-kB的核转位， 艾滋病毒感染。 这一过程由诱导激酶调节， 使IkBa在S32/36处磷酸化。 这些工作人员发现了一种诱导性的 巨噬细胞中的IkBa激酶，酪蛋白激酶II（PK-CK 2）。 的首要目标 该建议是表征NF-kB的分子机制， 参与调节HIV在人巨噬细胞中的持久性。 的 目的是：1）表征分子组成和调控 组成型NF-kB（RelB）活性及其与病毒复制的相关性; 2)研究HIV依赖性激活诱导池的机制 通过IkBa靶向NF-kB;和3）表征NF-kB的功能， 诱导型IkBa激酶及其与PK-CK 2的关系。