Abstract

The complement inhibitor CD55/DAF is expressed on many cell types. Dysregulation of CD55 expression is associated with increased disease severity in influenza A infection and vascular complications in pathologies that involve excessive activation of the complement system. A luciferase reporter system was used to functionally analyze the single nucleotide polymorphism rs2564978 in the U937 human promonocytic cell line. The polymorphism is in the promoter of the CD55 gene, and its minor allele T is associated with a severe course of influenza A(H1N1)pdm09. A decreased activity of the CD55 promoter carrying the minor rs2564978(T) allele was observed in activated U937 cells, which provide a cell model of human macrophages. Using bioinformatics resources, PU.1 was identified as a potential transcription factor that may bind to the CD55 promoter at the rs2564978 site in an allele-specific manner. The involvement of PU.1 in modulating CD55 promoter activity was verified by a PU.1 genetic knockdown with small interfering RNAs under specific monocyte activation conditions.

中文翻译：

---

与严重甲型流感相关的 rs2564978(T) 等位基因破坏巨噬细胞中骨髓分化因子 PU.1 的结合位点并降低 CD55/DAF 基因启动子活性

摘要

补体抑制剂 CD55/DAF 在许多细胞类型中表达。 CD55 表达失调与甲型流感感染的疾病严重程度增加以及涉及补体系统过度激活的病理学血管并发症有关。使用荧光素酶报告系统对U937人早核细胞系中的单核苷酸多态性rs2564978进行功能分析。该多态性位于CD55基因的启动子中，其次要等位基因 T 与 A(H1N1)pdm09 流感的严重病程相关。在活化的 U937 细胞中观察到携带次要 rs2564978(T) 等位基因的CD55启动子活性降低，该细胞提供了人类巨噬细胞的细胞模型。利用生物信息学资源，PU.1 被鉴定为一种潜在的转录因子，可以以等位基因特异性方式与 rs2564978 位点的CD55启动子结合。 PU.1 参与调节CD55启动子活性通过在特定单核细胞激活条件下使用小干扰 RNA 进行 PU.1 基因敲除得到验证。