登革病毒（DENV）引起的登革出血热（DHF）和登革休克综合症（DSS）死亡率高，存在血管内皮细胞（VECs）功能失调。我们发现DENV可直接诱导VECs凋亡，感染中产生大量的炎性细胞因子（CK）也损伤VECs，研究CK时发现let-7e表达增高,生物信息学分析发现表观调控分子EZH2和抑炎细胞因子IL-10为其靶基因。为深入研究let-7e 在炎性CK产生和调控中的作用，我们拟检测DENV未感染者、急性期感染者和康复者血清中的炎性CK、IL-10和let-7e，探讨CK与let-7e的关系；用不同来源PBMC感染DENV，分别检测淋巴细胞和单核细胞的CK和let-7e表达,分析CK及let-7e来源;建立let-7e高表达和低表达细胞系，用DENV感染后检测EZH2和CK，确定let-7e是通过表观调控作用还是直接作用而影响CK产生，阐明let-7e对CK产生的调控通路。研究结果将为登革热提供新的治疗靶点。

Both dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) are severe dengue virus (DENV) infections with high mortality rate and dysfunction of endothelial cells (VECs). Our group found that DENV can induce apoptosis of VECs and proinflammatiory cytokines (CKs) produced by DENV infection is the key factor for VECs damage. Increased expression of let-7e was also found in PBMCs after DENV infection. EZH2, a epigenetic regulator, and IL-10 were found as its target genes by bioinformation analysis. To further study on the role of let-7e in the mechanism of generation and regulation of proinflammatiory CKs, we will detect the expression of CKs and let-7e from serum of uninfected persons, the persons in the acute phase of DENV infection and those in Convalescence to explore the relationship between CKs and let-7e. Peripheral blood mononuclear cells (PBMCs) from those persons will be infected by DENV and the expression of CKs and let-7e will be detected in lymphocytes and monocytes. The cell lines with high expression or low expression of let-7e will be constructed. The expression of EZH2 and CKs will be detected after DENV infection. It will be helpful to investigate the regulatory pathway of let-7e on CKs production in DENV infection. The results will provide new therapeutic targets for dengue fever.