人巨细胞病毒miR-US33-5p通过下调HCMV UL16影响NK细胞活性

As the only beta-herpesvirus found to express miRNAs, Human cytomegalovirus (HCMV) encodes for at least 26 microRNAs (miRNA). These miRNAs are utilized by HCMV to regulate its own genes as well as the genes of the host cell during infection to achieve virus replication, immune evasion and so on. miRNA-US33-5p is one of original discovered HCMV miRNA, it is almost absent during HCMV latency, but has a relatively high expression when reactivation of the virus or productive infection. It has been reported that over-expression of miR-US33 can inhibit the lytic viral replication. Our previous research had explained the molecular mechanism of how miR-US33-5p down regulates virus replication. At the same time, HCMV UL16 gene had found to be another candidate target gene of miR-US33-5p. It has been reported that HCMV glycoprotein UL16 can inhibits NK cell cytotoxicity. The project prepares to study if miR-US33-5p can be used to facilitate HCMV to enter a latent state by down regulation of HCMV UL16 expression using HCMV BAC, flow cytometry, immunoblotting, MTT assay on the base of cellular and animal models.

人巨细胞病毒（HCMV）是目前唯一被证实具有编码microRNA(miRNA)能力的β疱疹病毒，编码至少26种成熟miRNA。HCMV利用这些miRNA调节自身及宿主细胞的基因表达完成病毒复制、免疫逃避等过程。作为最早发现的HCMV编码的miR之一，miRNA-US33-5p在HCMV潜伏感染时并不表达，而潜伏再激活及活动感染时表达丰度较高。有文献指出miR-US33能抑制病毒复制，本研究前期工作阐释了miR-US33-5p抑制病毒复制的分子机制。同时发现miR-US33-5p另外一个候选靶基因HCMV UL16，它编码一种糖蛋白，参与病毒逃避NK细胞杀伤。本项目拟在细胞及动物模型基础上，采用HCMV细菌人工染色体、流式细胞术、免疫印迹、MTT还原法等材料方法，深入研究miRNA-US33-5p是否通过抑制病毒自身编码的UL16基因表达，控制HCMV活动感染，并促使病毒进入潜伏感染状态。