人巨细胞病毒先天感染危害巨大，并引起免疫抑制患者致死性感染。其危害主要来自于潜伏病毒在孕期等特定时期的再激活。搞清病毒潜伏状态维持及再激活机制并建立有效的病毒再激活控制手段是预防人巨细胞病毒危害的关键。目前，已经证明人巨细胞病毒潜伏感染过程中UL138及LUNA基因处于高表达状态，并与病毒潜伏感染的形成与维持密切相关。但UL138及LUNA基因在潜伏感染过程中高表达的转录调控机制尚不清楚。本项目拟通过分析UL138及LUNA基因的转录调控元件、相关转录因子及转录调控因子、以及这些因子在病毒敏感细胞与潜伏感染细胞中分布的差异，找出在潜伏感染细胞中针对病毒潜伏感染形成与维持起决定作用的UL138及LUNA基因的转录因子及转录调控因子，进一步研究这些因子在不同细胞中的表达改变对病毒感染状态改变的作用。本项目将为阐明人巨细胞病毒潜伏感染机制、建立有效的潜伏病毒再激活干预手段积累资料，具有重要意义。

Infection of human cytomegalovirus (HCMV) in immunocompromised patients is a significant cause of morbidity and mortality. HCMV represents a major cause of disease in transplant patients, AIDs sufferers and newborns. The main source of HCMV infection in these patients is from reactivation of latent virus during special period, such as pregnancy. Knowledge about the mechanism of formation, maintenance and reactivation of latent HCMV infection, and establishment of powerful methods for inhibiting HCMV reactivation are key steps for prevention of HCMV infection. In 2007, Felicia Goodrum et al firstly reported that HCMV UL138 ORF was required for HCMV to establish and/or maintain a latent infection in hematopoietic progenitor cells infected in vitro [Blood, 2007, 110: 937-945]. In 2005, Mariana Bego et al reported a novel transcript, UL81-82ast, UL81-82 antisense transcript, and its protein product [J. Virol., 2005, 79(17); 11022-11034]. And the latent gene transcript UL81-82ast was named as latency unique natural antigen (LUNA) [Arch Virol. 2011, 156:1847-1851]. So far, it has been confirmed that the UL138 and LUNA genes were highly expressed during HCMV latent infection, and the expressions were closely associated with formation and maintenance of HCMV latent infections [J. Virol., 2009, 83(11); 5615-5629; PLoS Pathogens, 2011, 7(12); e1002444; J. Virol., 2011; 85(21): 11409-11421; J. Virol. 2012; 86(16): 8653-62; J. Gen. Virol., 2010; 91: 599-604]. Although two reports have discussed the putative promoter of UL138 and LUNA during productive infection[J. Virol., 2010, 84(18): 9472-9486; J.Virol., 2010, 84(14); 7185-7194;], and one recent report has demonstrated that LUNA is regulated by the myeloid transcription factor GATA-2[J. Virol. 2013, PMID: 23365437], it is still unclear about the transcriptional mechanism of the UL138 and LUNA genes. In this study, we plan to analyze the transcriptional regulation elements of the UL138 and LUNA genes, such as promoter, enhancer and inhibitor, identify the related transcription factors and transcriptional regulation factors corresponding to the transcriptional regulation elements of the UL138 and LUNA genes, and detect the different distributions of these factors between virus sensitive cells (human embryo lung fibroblast) and latently infected cells (CD34+ hematopoietic progenitor cells, HPCs, or Kasumi-3 cells) [J. Virol, 2012; 86(18): 9854-9865]. The aim of this study is to find the UL138 and LUNA related transcription factors and transcriptional regulation factors, which have determinant role on HCMV latency in latently infected cells, and to study the effects of expression changes of these factors on virus infection stages (productive or latent infections). This project will accumulate data for understanding the mechanism of HCMV latent infection, and help to establish a powerful prevention means for inhibiting HCMV reactivation. It should have both theological and actual meanings for HCMV preventions.