microRNA在B组柯萨奇病毒持续感染心肌细胞中的作用

项目名称： microRNA在B组柯萨奇病毒持续感染心肌细胞中的作用

项目编号： No.30872231

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 轻工业、手工业

项目作者： 钟照华

作者单位： 哈尔滨医科大学

项目金额： 33万元

中文摘要： B组柯萨奇病毒（CVB）是病毒性心肌炎的主要病原，可引起扩张型心肌病。miRNA是非编码RNA，可作用于mRNA发挥转录后调控作用。CVB基因组是单正链RNA，其转录和翻译可能受到miRNA调控。本研究发现：①iR-342-5p可显著抑制CVB 3型（CVB3）复制，其作用机制是直接作用于CVB3的2C蛋白编码区，其靶点在CVB其他型别保守，故对其他型别有相同作用，miR-342-5p可能成为抗CVB感染的核酸类药物；②iR-10a*可上调CVB3复制，其作用靶点位于CVB3的3D编码区，miR-10a*在CVB3感染心肌早期起重要调控作用。miRNA的星链可上调靶基因表达是miRNA调控作用的一个新机制；③#25972;合报告基因EGFP或mCherry的CVB3重组毒株基因组不稳定，仅适合短期细胞学实验研究；④iR-122可上调肝细胞凋亡，其低表达可能是肝细胞癌发生的机制之一。综上，本课题证明了miRNAs可以转录后阶段调控CVB在细胞复制，为防治CVB感染提供新的靶点和策略。

中文关键词： miR-352-5p; miR-10a*; B组柯萨奇病毒; 病毒复制; 病毒感染

英文摘要： Coxsackieviruses B (CVBs) are the major pathogens of viral myocarditis that leads to dilated cardiopyopathy. miRNAs are non-coding RNAs that can post-transcriptionally modulate mRNA translation. The CVBs genomes are positive single-stranded RNAs that may be potential targets of miRNAs. This study demonstrates that (1) miR-342-5p could significantly inhibit the CVB3 replication through directly targeting the 2C-coding region of CVB3. The target sequence was highly conserved in all CVB types, thus, miR-342-5p could inhibit the biosynthesis of all CVB types. miR-342-5p may be a potential RNA drug for anti-CVBs infection. (2) miR-10a* could significantly upregulate the replication of CVB3 by directly interacting with the 3D-coding region. miR-10a* may play a key regulator role in the early CVB3 infection in myocardial cells. miRNA star strand upregulating gene expression is a newly recognized mechanism of the gene expression modulation of miRNAs. (3) The genomes of recombinant CVB3 integrated with EGFP- or mCherry-coding sequences were not stable. These CVB3 variants can only be used for short-term in vitro studies. (4) miR-122 could promote the hepatocellular apoptosis. The down-regulated miR-122 expression may be one of the carcinogenic mechanisms of hepatocarcinoma. Taken together, This research demonstrates that miRNAs can post-transcriptionally modulate the CVB replication. The modulation of miRNAs may be a new target for the therapy and prevention of CVBs infection.

英文关键词： miR-243-5p; miR-10a*; coxsackievirus B; Viral replication; Viral infection