临床输血与检验2025，Vol.27Issue(3)：329-339,11.DOI:10.3969/j.issn.1671-2587.2025.03.009
miR-4454通过靶向LRPAP1激活Ⅰ型干扰素信号通路抑制寨卡病毒复制
MiR-4454 Inhibits Zika Virus Replication by Targeting LRPAP1 and Activating the Type Ⅰ Interferon Signaling Pathway
摘要
Abstract
Objective This study aims to investigate the specific regulatory effect of miR-4454 on ZIKV replication and reveal its potential molecular mechanisms,providing new ideas and targets for the treatment of ZIKV infection.Methods Cells were transfected with miR-4454 mimics or inhibitors and subsequently infected with ZIKV.The expression of ZIKV NS5 mRNA and NS1 protein was measured using qRT-PCR and Western blot analyses.Bioinformatics tools were employed to predict potential target genes of miR-4454,focusing on the validation of LRPAP1(low-density lipoprotein receptor-related protein associated protein 1)as a downstream target.Following the transfection of LRPAP1 plasmid or si-LRPAP1 into cells,ZIKV infection was performed,and qRT-PCR was used to detect ZIKV NS5 mRNA and interferon-stimulated gene expression,while Western blotting assessed the levels of ZIKV NS1 protein,IFNAR1,and phosphorylated STAT1,to explore the effect of LRPAP1 expression changes on ZIKV replication and the Type Ⅰ interferon signaling pathway.Results Overexpression of miR-4454 in cells inhibited the replication of ZIKV NS5 mRNA and expression of NS1 protein.Bioinformatics prediction identified LRPAP1 as a potential target of miR-4454,which is related to viral infection and the Type Ⅰ interferon signaling pathway.Dual-luciferase reporter assays confirmed that LRPAP1 is a direct target of miR-4454.Overexpression of LRPAP1 promoted ZIKV replication and suppressed the Type Ⅰ interferon signaling pathway,while knockdown of LRPAP1 inhibited ZIKV replication and activated this signaling pathway.Conclusion miR-4454 modulates ZIKV infection through the intrinsic immune pathway,suggesting its potential as a therapeutic target and providing new insights for the development of related treatment strategies.关键词
寨卡病毒/非编码RNA/miR-4454/Ⅰ型干扰素信号通路Key words
Zika virus/Non-coding RNA/MiR-4454/Type Ⅰ interferon signaling pathway分类
医药卫生引用本文复制引用
韦芊芊,陈利民,李玉佳,李世林..miR-4454通过靶向LRPAP1激活Ⅰ型干扰素信号通路抑制寨卡病毒复制[J].临床输血与检验,2025,27(3):329-339,11.基金项目
本课题受四川省自然科学基金(面上)项目(No.2025ZNSFSC0678)资助 （面上）
