Regulation of MicroRNA by Human Cytomegalovirus

人类巨细胞病毒对 MicroRNA 的调控

• 批准号: 7499628
• 负责人: PHILIP E PELLETT
• 金额: $ 22.58万
• 依托单位: WAYNE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-09-30 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7499628
• 关键词: Apoptosis; Biological; Biology; Cell Cycle; Cell physiology; Cells; Class; Complement; Complex; Cytomegalovirus; Cytomegalovirus Infections; Defense Mechanisms; Development; Diagnostic Procedure; Ensure; Environment; Exercise; Gene Expression; Genes; Genetic; Genome; Hematopoietic stem cells; Herpesviridae; Homologous Gene; Human; Human Genome; Immune response; Individual; Infection; Lymphocyte; Mediating; Metabolism; MicroRNAs; Neurons; Outcome; Population; Proteins; RNA; Range; Regulation; Research; Rest; Role; Simplexvirus; Small Interfering RNA; Staging; Stem cells; Time; Transcript; Translations; Viral; Virus; Work; cell growth regulation; cell type; improved; novel therapeutics; pathogen; success; transmission process

DESCRIPTION: MicroRNAs (miRNA) are recently discovered small (-21 nt) RNA species that have important roles in regulation of cellular gene expression. This is to be distinguished from mechanistically related cellular defense mechanisms that are mediated via very similar mechanisms (small interfering RNA, or siRNA), but target exogenous mRNAs, such as those expressed by viruses. The human genome has been predicted to encode as many as 500 to 600 distinct miRNA genes. Targets of miRNA regulation include genes involved in regulation of developmental stages and in cellular differentiation. Different cell types, e.g., neuronal vs. stem cells, express miRNA populations that differ in representation and abundance of individual miRNA species. miRNA activity is manifest as reduced translation from the targeted mRNAs. Herpesviruses are genetically complex viruses that encode as many as 200 genes, of which only about 40 are involved in the fundamental aspects of replicating and packaging the genome for transmission. The remainder are involved in manipulating the cellular and organismal environment to ensure short-term replicative success and virus survival on an evolutionary time scale. Thus, these gene products exercise diverse and profound effects on regulation of host cell metabolism and immune responses. Human cytomegalovirus (HCMV) is an important human pathogen that has one of the genetically most complex herpesvirus genomes, and a correspondingly complex biology. This application is aimed at understanding the relationships between HCMV infection and the expression and function of cellular miRNA genes. We propose two lines of inquiry: Aim 1: Does HCMV infection result in altered expression of cellular miRNA species? Aim 2: What are the biological consequences of virally altered miRNA expression? The significance of the work proposed here rests on it opening a new avenue of research relating to viral use and manipulation of a cellular process that regulates a wide range of outcomes. Potential long-term outcomes of this work include improved diagnostic methods and novel therapeutic strategies.

描述：MicroRNA (miRNA) 是最近发现的小 (-21 nt) RNA 种类，在调节细胞基因表达中发挥重要作用。这与机械相关的细胞防御机制不同，后者通过非常相似的机制（小干扰 RNA 或 siRNA）介导，但靶向外源 mRNA，例如病毒表达的 mRNA。据预测，人类基因组可编码多达 500 至 600 个不同的 miRNA 基因。 miRNA 调控的靶标包括参与发育阶段和细胞分化调控的基因。不同的细胞类型，例如神经元细胞与干细胞，表达的 miRNA 群体在个体 miRNA 种类的代表性和丰度方面有所不同。 miRNA 活性表现为目标 mRNA 的翻译减少。疱疹病毒是遗传复杂的病毒，编码多达 200 个基因，其中只有约 40 个基因参与复制和包装基因组以进行传播的基本方面。其余的参与操纵细胞和有机体环境，以确保短期复制成功和病毒在进化时间尺度上的存活。因此，这些基因产物对宿主细胞代谢和免疫反应的调节发挥着多样而深远的影响。人类巨细胞病毒（HCMV）是一种重要的人类病原体，具有遗传上最复杂的疱疹病毒基因组之一，以及相应复杂的生物学特性。本申请旨在了解HCMV感染与细胞miRNA基因表达和功能之间的关系。我们提出两条线索： 目标 1：HCMV 感染是否会导致细胞 miRNA 种类的表达改变？目标 2：病毒改变 miRNA 表达的生物学后果是什么？这里提出的工作的重要性在于它开辟了一条新的研究途径，涉及病毒的使用和细胞过程的操纵，从而调节广泛的结果。这项工作的潜在长期成果包括改进的诊断方法和新颖的治疗策略。