人巨细胞病毒miR-UL112-1初级转录结构及转录调控机制的研究

项目名称： 人巨细胞病毒miR-UL112-1初级转录结构及转录调控机制的研究

项目编号： No.81201274

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学四处

项目作者： 黄郁晶

作者单位： 中国医科大学

项目金额： 23万元

中文摘要： 人巨细胞病毒（HCMV）是引起先天感染和出生缺陷的主要病原体之一，可造成多系统多器官疾病和畸形，危害巨大。HCMV先天感染的致病机理尚不清楚。近年研究发现，HCMV是唯一具有编码并表达microRNA功能的人类β疱疹病毒，这一重要发现为我们对HCMV致病机理的深入研究提供了全新的思路。在前期研究中，我们在进一步证明HCMV miR-UL112-1具有调节宿主细胞多种免疫因子表达的重要功能的基础上，首次证实 miR-UL112-1具有不同片段长度的多种初级转录形式，由此提示miR-UL112-1的表达可因初级转录本结构的不同而存在多种不同的转录调控方式，以实现其在病毒特定感染时期的特异性表达及病毒对不同免疫状态宿主的适应性。本研究将从病毒编码microRNA的初级转录结构及转录调控机制这个全新的层面深入解读HCMV的致病机理，对预防及治疗HCMV感染，进而减少HCMV致畸儿出生具有重要意义。

中文关键词： 人巨细胞病毒；miR--UL112-1；初级转录；转录调控；

英文摘要： Human cytomegalovirus (HCMV) is a ubiquitous herpesvirus that infects a broad range of cell types in its human host, contributing to its complex and varied pathogenesis. It is one of the main pathogens causing congenital infection and birth defects. The pathogenic mechanism of HCMV congenital infection still remains unclear at present. microRNAs (miRNAs) are an abundant class of small non-coding RNA molecules that regulate gene expression at the posttranscriptional level. Recent studies have shown that HCMV is the only human β-herpesvirus found to express miRNAs. The important finding provides a new avenue of the investigation for HCMV pathogenic mechanism. It is conceivable that HCMV encoded miRNAs are exploited during virus immune evasion.The major histocompatibility complex class 1-related chain B (MICB) has been identified as a functional target of HCMV miR-UL112-1. miR-UL112-1-mediated down-regulation of MICB perturbed MICB binding with NKG2D and reduced killing of HCMV infected cells by NK cells. In our previous research, HCMV miR-UL112-1 has been furhter proven to play an important role in HCMV immune evasion by targeting mRNA sequences of interleukin 32 (IL-32) and NFkB activating protein. In addition, it was confirmed for the first time that HCMV miR-UL112-1 possessed alternative transcripts in differ

英文关键词： HCMV；miR-UL112-1；primary transcription；transcriptional regulation；