HCMV是围产期感染的常见病原体，最新研究表明其编码的lncRNA4.9与潜伏感染密切相关，但机制未明。我们前期工作已证实lncRNA4.9通过抑制NAB2而上调EGR1的表达。在此基础上，本项目以HCMV潜伏感染的CD14+细胞为研究模型，首先分别调控lncRNA4.9和NAB2的表达，监测病毒潜伏状态，免疫共沉淀和质谱分析EGR1的结合蛋白，探明lncRNA4.9通过调控EGR1-IE2对HCMV潜伏感染的作用；然后分别调控lncRNA4.9和TGF-β的表达，检测细胞周期变化，进一步与T细胞共培养后检测免疫因子和T细胞活化水平，明确lncRNA4.9通过调控TGF-β对HCMV潜伏感染的影响；最后，抑制/激活T细胞并与潜伏感染细胞共培养，监测病毒潜伏状态，揭示免疫激活对HCMV潜伏感染的影响。本项目将为阐明HCMV潜伏感染的发病机制提供新思路，为HCMV防治药物的研发提供新靶标。

Human cytomegalovirus (HCMV) is the most common cause of perinatal infections. Recent study has shown that long noncoding (lnc) RNA4.9 encoded by HCMV may be closely related to viral latent infection, but the mechanisms remain poorly understood. In preliminary experiment, we predicted and verified lncRNA4.9 could up-regulate the expression of early growth response gene 1 (EGR1) by targeted inhibition on NGFI-A binding protein 2 (NAB2). In this study, a previously constructed model of HCMV latency by infecting CD14+ monocyte will be used to explore the effects of lncRNA4.9 on HCMV latency and the regulatory mechanisms. Firstly, basing on the respective regulation of lncRNA4.9 and NAB2 levels, the expressions of lncRNA4.9, NAB2, EGR1 would be detected, the changes of HCMV latent state would be monitored, and the specific protein combinating to EGR1 would also be immune co-precipitated and mass spectrometry analyzed to reveal the effect of lncRNA4.9 on HCMV latency by regulating EGR1-IE2. Secondly, the changes of cell cycle would be detected after the respective regulation on the expressions of lncRNA4.9 and TGF-β. Furthermore, the levels of immune factors and T cell activation would be detected, and the changes of HCMV latent state would be monitored in a co-culture model of HCMV latently infected cells with T lymphocytes to identify the effect of lncRNA4.9 on HCMV latency by regulating TGF-β to inhibit cell cycle and T cell functions. Finally, basing on the co-culture model of HCMV latently infected cells with inhibited/activated T lymphocytes, the levels of immune factors and T cell activation would be detected, and the lncRNA4.9 expression and the changes of HCMV latent state would be monitored to interpret the effect of immune activation on HCMV latency. This study will be helpful to provide novel ideas on the pathogenesis of HCMV latent infection and new targets of drug development for HCMV treatment and prevention.