肾综合征出血热患者急性期外周血CD226dim炎性单核细胞抗病毒功能受损机制的研究

汉滩病毒（HTNV）感染引起的肾综合征出血热（HFRS）是危害极大的急性传染病。HFRS患者单核细胞表型和功能的改变，影响免疫系统早期对HTNV的识别及清除，进而影响病情。我们首次发现，HFRS患者急性期外周血出现CD226dim炎性单核细胞（iMo），且危重型患者CD226dim iMo比例显著高于中型/重型患者；至恢复期，CD226dim iMo消失，恢复至正常人iMo表型CD226hi。预实验结果提示HFRS患者CD226dim iMo抗病毒功能减弱。本项目拟明确CD226dim iMo是否由HTNV感染iMo产生；同时研究CD226dim和CD226hi iMo抗病毒相关功能，筛选决定两亚群抗病毒功能差异的信号转导分子。本项目研究为阐明单核细胞应答在HFRS发病中的作用以及HFRS发病机制提供重要的实验依据，并可能为早期控制HTNV复制及减轻HFRS患者临床症状提供新的靶点和策略。

Hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus (HTNV) is a serious acute infectious disease. The phenotype and function changes of monocytes during the early phase of HFRS influence the recognition and elimination of HTNV by immune system, which has an impact on the disease severity. The phenotype of normal controls’ inflammatory monocytes (iMo) is CD226hi. Here, we firstly found that a novel CD226dim iMo subset appeared at the acute phase of HFRS and disappeared in the convalescent phase, and the proportion of CD226dim iMo was significantly increased in the acute phase of patients with critical HFRS than that in patients with moderate/severe HFRS. Preliminary experimental results suggested the antiviral function of CD226dim iMo was reduced compared with CD226hi iMo. In this project, we will confirm whether the CD226dim iMo is produced by HTNV infecting iMo, and study the antiviral function of CD226dim and CD226hi iMo. Then screen the signal transduction molecules which determine the differences of antiviral function of CD226dim and CD226hi iMo. The study will contribute to illuminating the function of monocyte responses in HFRS and the mechanism of HFRS pathogenesis, and may provide new targets and strategies to control HTNV infection in the early stage and alleviate disease severity of patients with HFRS.