Regulation of HIV infection by Methamphetamine and non-coding RNAs

甲基苯丙胺和非编码 RNA 调控 HIV 感染

基本信息

批准号：
8610908
负责人：
TARIQ M RANA
金额：
$ 9.12万
依托单位：
SANFORD BURNHAM PREBYS MEDICAL DISCOVERY INSTITUTE
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-07-15 至 2014-07-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8610908
关键词：
3&apos Untranslated Regions AIDS/HIV problem Acquired Immunodeficiency Syndrome Affect Affinity Antiviral Agents Attention Binding Biology Boxing Cells Communicable Diseases Complex Cytoplasm DDX6 gene Data Defense Mechanisms Dendritic Cells Disease Outcome Disease Progression Exposure to Functional RNA Gene Expression Profile Genes Genome Goals HIV HIV Infections HIV-1 Human Human Genome Human Pathology Immune Immune response Immunity Infection Invertebrates Knowledge Life Cycle Stages Mammals Mediating Messenger RNA Methamphetamine Methodology MicroRNAs Molecular Myeloid Cells Natural Immunity Neurocognitive Neurotransmitters Phagocytosis Physiological Processes Plants Play Predisposition Process Production Proteins Publishing RNA RNA Interference RNA-Induced Silencing Complex Rana Regulation Repression Retroviridae Ribonucleoproteins Risk Role Serotonin Short-Term Memory Site Small Interfering RNA Specificity Structure Study Section System T-Lymphocyte Technology Translational Repression Translations Untranslated Regions Viral Viral Pathogenesis Virus Diseases Work antigen processing base design dopamine transporter executive function helicase insight interdisciplinary approach macrophage methamphetamine abuse methamphetamine exposure nanoparticle next generation sequencing novel therapeutics pathogen programs public health relevance recreational drug use research study response screening unpublished works

项目摘要

DESCRIPTION (provided by applicant): PROJECT SUMMARY Although non-coding RNAs comprise a majority of the human transcriptome, there remain critical gaps in our knowledge of the role of these molecules in most human pathologies, including HIV/AIDS. Here, we propose to decipher the mechanisms of non-coding RNAs, and their associated ribonucleoprotein complexes, in regulating HIV-1 infection of primary macrophages, particularly after exposure to Methamphetamine (METH). These studies will build on a powerful set of preliminary data that implicate several short and long non-coding RNAs in the regulation of HIV and response to METH. We propose to integrate several state-of-the-art post-genome technologies and newly developed experimental methodologies, including next generation sequencing and nanoparticle delivery systems, to provide important insights into the activity of these molecules in both promoting and restricting HIV replication. These analyses are designed to comprehensively identify non-coding RNAs that regulate these processes in primary human macrophages, and experimentally delineate their cellular or viral targets. Taken together, these studies will provide significant knowledge towards the molecular and cellular mechanisms underlying RNA-based host-pathogen interactions and antiviral functions.

描述（由申请人提供）：项目摘要尽管非编码 RNA 构成了人类转录组的大部分，但我们对这些分子在大多数人类病理学（包括 HIV/AIDS）中的作用的了解仍然存在严重差距。在这里，我们建议破译非编码RNA及其相关核糖核蛋白复合物在调节原代巨噬细胞的HIV-1感染中的机制，特别是在暴露于甲基苯丙胺（METH）后。这些研究将建立在一组强有力的初步数据的基础上，这些数据表明几种短非编码RNA和长非编码RNA参与HIV的调节和对METH的反应。我们建议整合几种最先进的后基因组技术和新开发的实验方法，包括下一代测序和纳米颗粒递送系统，以提供有关这些分子在促进和限制 HIV 复制方面的活性的重要见解。这些分析旨在全面鉴定在原代人类巨噬细胞中调节这些过程的非编码RNA，并通过实验描述其细胞或病毒靶点。总而言之，这些研究将为基于 RNA 的宿主-病原体相互作用和抗病毒功能的分子和细胞机制提供重要的知识。