HIV AND NF-KB INTERACTIONS IN MONOCYTES

说明(改编自提案)巨噬细胞在 艾滋病毒感染的发病机制，因为它们是主要的 病毒在整个感染过程中持续复制。然而， 调节病毒持久性的机制仍未确定。这个 核因子-kB/Rel转录因子家族在HIV转录中起重要作用 和巨噬细胞的复制。核因子-kB的活性在肝细胞癌中具有结构性。 巨噬细胞的核，以RelB的形式存在，以胞浆和 与IKB相关的可诱导性核因子-kB池(p50/65)。来自本实验室的研究 已经确定了巨噬细胞特有的核因子-kB成分，这 包括靶向IkBA和核转录因子-kB的核转位 艾滋病毒感染。这一过程是由诱导的激酶调节的， 使S32/36处的IkBA磷酸化。这些工人已经确定了一种诱因 巨噬细胞中的IkBA激酶，酪蛋白激酶II(PK-CK2)。的主要目标是 这项提议是为了表征核因子-kB通过 参与调节HIV在人巨噬细胞中的持久性。这个 目的是：1)表征分子组成和调节 组成性核因子-kB(RelB)活性及其与病毒复制的相关性； 2)研究HIV依赖的诱导池的激活机制 通过IkBA靶向表达核因子-kB；3)表征核因子-kB的功能。 诱导型IkBAK及其与PK-CK2的关系

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.