南京医科大学学报（自然科学版）2026，Vol.46Issue(1)：47-54,67,9.DOI:10.7655/NYDXBNSN250914
多聚胞嘧啶结合蛋白2在大别班达病毒感染中的作用及机制
Role and mechanisms of poly(C)-binding protein 2 in Dabie Banda virus infection
摘要
Abstract
Objective:To investigate the role of poly(C)-binding protein 2(PCBP2)in the pathogenic process following Dabie Banda virus(DBV)infection and its mechanism of action through the regulation of ferroptosis.Methods:The THP-1 human monocytic cell line was used as a model,the mitochondrial structural changes under viral infection were observed via transmission electron microscopy.Lentivirus-mediated PCBP2-overexpressing and lentivirus-mediated PCBP2-knockdown THP-1 cell lines were constructed.FerroOrange fluorescent probe was used to measure Fe2+levels,2,7-dichlorofluorescein diacetate(DCFH-DA)assay was employed to determine reactive oxygen species(ROS)levels,and Western blot was performed to assess the expression of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4)proteins,thus to evaluate the impact of PCBP2 modulation on ferroptosis.Cells were treated with ferroptosis inducers(RSL3,erastin)and inhibitors(Fer-1,Lip-1).Viral replication levels were examined by qRT-PCR and immunofluorescence to explore whether PCBP2 influences DBV replication by regulating ferroptosis.Results:In DBV-infected cells,both mRNA and protein levels of PCBP2 were significantly downregulated.DBV infection induced typical ferroptosis features,including mitochondrial cristae reduction and swelling.PCBP2 knockdown and overexpression in THP-1 cells were confirmed by qRT-PCR and Western blot.PCBP2 knockdown decreased the expression of ferroptosis-related genes of solute carrier family 7 member 11(SLC7A11)and glutathione peroxidase 4(GPX4),leading to increased ROS and Fe2+levels.Conversely,PCBP2 overexpression elevated SLC7A11 and GPX4 expression while reducing ROS and Fe2+accumulation.The 50%tissue culture infective dose and protein level assays further demonstrated that ferroptosis inducers partially counteracted the pro-viral effect of PCBP2 overexpression,while ferroptosis inhibitors partially reversed the antiviral effect caused by PCBP2 knockdown.Conclusion:This study reveals that PCBP2 inhibits ferroptosis by maintaining the SLC7A11/GPX4 system,thereby restricting DBV replication.These findings not only elucidate the regulatory role of PCBP2 in DBV infection but also provide novel insights into the pathogenesis of severe fever with thrombocytopenia syndrome(SFTS).Moreover,targeting the PCBP2-ferroptosis pathway may represent a potential therapeutic strategy for SFTS,offering new directions for antiviral drug development.关键词
发热伴血小板减少综合征/大别班达病毒/铁死亡/多聚胞嘧啶结合蛋白2/病毒复制Key words
severe fever with thrombocytopenia syndrome/Dabie Banda virus/ferroptosis/poly(C)-binding protein 2/viral replication分类
医药卫生引用本文复制引用
YU Xinyi,DAI Yan,SHI Mengqi,PU Qinqin,HU Nannan,JIN Ke,LI Jun..多聚胞嘧啶结合蛋白2在大别班达病毒感染中的作用及机制[J].南京医科大学学报（自然科学版）,2026,46(1):47-54,67,9.基金项目
国家自然科学基金(81871242) （81871242）
