军事医学2025,Vol.49Issue(1):27-34,8.DOI:10.7644/j.issn.1674-9960.2025.01.005
脂氧合酶通过负调控自噬抑制新型布尼亚病毒感染
Lipoxygenase inhibits SFTSV replication by down-regulating autophagy
摘要
Abstract
Objective To explore the effects of lipoxygenase(LOX)on severe fever with thrombocytopenia syndrome virus(SFTSV)in human umbilical vein endothelial cells(HUVECs).Methods The CCK-8 assay was used to assess the cytotoxicity of LOX in HUVECs.Real-time quantitative PCR(qPCR)was adopted to detect the replication of viral RNA in cells.The infection rate of SFTSV to HUVECs was observed via indirect immunofluorescence assay(IFA).The expressions of intracellular viral NP protein and autophagy related proteins microtubule-associated protein 1 light chain 3(LC3)and adenosine 5'-monophosphate-activated protein kinase(AMPK)/mammalian target of rapamycin(mTOR)were detected via Western blotting.Lipid metabolomics was used to analyze the differences in expressions of intracellular metabolites in the SFTSV-infected Huh 7 with or without LOX treatment.Results The results of CCK-8 showed no obvious cytotoxicity to HUVECs with LOX≤8 mg/mL.With the increase of LOX concentrations,the viral RNA level,viral infection rate,and expressions of SFTSV nucleoprotein(NP)protein were gradually decreased,respectively.The autophagy reaction was activated in SFTSV-infected HUVECs,evidenced by the increased expression level of LC3 Ⅱ protein.Compared with the untreated group,LOX treatment resulted in decreased levels of LC3 Ⅱ and AMPK phosphorylation,and enhanced phosphorylation of mTOR in SFTSV-infected HUVEC.Conclusion LOX negatively regulates autophagy by inhibiting AMPK/mTOR signaling pathway,thereby inhibiting SFTSV replication.关键词
发热伴血小板减少综合征病毒/脂氧合酶/自噬/AMPK/mTOR/人脐静脉内皮细胞Key words
severe fever with thrombocytopenia syndrome virus/lipoxygenase/autophagy/AMPK/mTOR/human umbilical vein endothelial cells分类
医药卫生引用本文复制引用
李爽,郑小杰,张运发,张灵玉,杨童,黎浩,张小爱,刘玮..脂氧合酶通过负调控自噬抑制新型布尼亚病毒感染[J].军事医学,2025,49(1):27-34,8.基金项目
国家自然科学基金项目(82330103) (82330103)