塞内卡病毒通过激活自噬降解FBXW7拮抗宿主的抗病毒应答  

Seneca valley virus antagonises host antiviral response by activating autophagy to degrade FBXW7

作　　者：向晗一 张瑞 林馨倩 林含睿 黄雄挺 周泷 张志东 李彦敏 XIANG Hanyi;ZHANG Rui;LIN Xinqian;LIN Hanrui;HUANG Xiongting;ZHOU Long;ZHANG Zhidong;LI Yanmin(Key Laboratory of Veterinary Medicine in Universities of Sichuan Province,Southwest Minzu University,Chengdu 610041,Sichuan,China)

机构地区：[1]西南民族大学动物医学四川省高校重点实验室,四川成都610041

出　　处：《微生物学通报》2024年第2期573-581,共9页Microbiology China

基　　金：中央高校基本科研业务费专项资金优秀学生培养工程项目(2022NYXXS023);西南民族大学“双一流”项目(XM2023012);四川省自然科学基金(2022NSFSC0073)。

摘　　要：【背景】塞内卡病毒(seneca valley virus,SVV)可引起猪严重的水疱性疾病,但目前仍无商业化疫苗,解析其与宿主抗病毒分子的相互作用具有重要意义。【目的】探究E3泛素连接酶(F-box and WD repeat domain containing 7,FBXW7)在抗SVV感染中的作用及其机制。【方法】利用小干扰技术敲低PK-15细胞FBXW7,结合RT-qPCR、组织半数感染量(tissue culture infective dose 50%,TCID50)和Western blotting分析FBXW7对SVV在PK-15细胞中复制及细胞因子的影响。【结果】Western blotting结果显示,SVV感染能够抑制PK-15细胞中FBXW7蛋白表达水平;敲低FBXW7后促进SVV复制,同时炎性细胞因子IL-6、IFN-β、TNF-αmRNA水平均显著降低;进一步研究显示,敲低ATG5抑制自噬后抑制FBXW7蛋白降解,SVV复制水平下降。【结论】本研究发现FBXW7对SVV复制具有抑制作用,SVV通过激活自噬介导FBXW7降解,为研发抗病毒靶点提供了新策略。[Background]Seneca valley virus(SVV)can cause severe blistering in pigs.Due to the lack of commercial vaccines,it is essential to probe into the interactions of SVV with host antiviral molecules.[Objective]To investigate the role of the E3 ubiquitin ligase,F-box and WD repeat domain containing 7(FBXW7),in anti-SVV infection.[Methods]The small interfering RNA(siRNA)was employed to knock down FBXW7.RT-qPCR,TCID50,and Western blotting were employed analyze the effect of FBXW7 on SVV replication and cytokines in PK-15 cells.[Results]Western blotting results showed that SVV infection down-regulated the expression of FBXW7 in PK-15 cells.The knockdown of FBXW7 promoted SVV replication and down-regulated the mRNA levels of interleukin-6(IL-6),interferon-β(IFN-β),and tumor necrosis factor-α(TNF-α).When ATG5 was knocked down to inhibit autophagy,FBXW7 protein degradation was inhibited and SVV replication decreased.[Conclusion]FBXW7 has an inhibitory effect on the replication of SVV which mediates FBXW7 degradation by activating autophagy.The finding provides a new strategy for the development of antiviral targets.

关 键 词：塞内卡病毒 FBXW7 自噬 细胞因子 

分 类 号：S852.65[农业科学—基础兽医学]