BMP4通过诱导ID1的上调表达抑制口蹄疫病毒的复制  

BMP4 inhibits foot-and-mouth disease virus replication by inducing ID1 upregulation

作　　者：姚凯慎 任亭亭 毛箬青[2] 殷相平[2] 孙跃峰 何俊峰[1] YAO Kai-shen;REN Ting-ting;MAO Ruo-qing;YIN Xiang-ping;SUN Yue-feng;HE Jun-feng(College of Veterinary Medicine,Gansu Agricultural University,Lanzhou 730070,China;State Key Laboratory of Veterinary Etiological Biology/Lanzhou Veterinary Research Institute,Chinese Academy of Agricultural Sciences,Lanzhou 730046,China)

机构地区：[1]甘肃农业大学动物医学院,甘肃兰州730070 [2]中国农业科学院兰州兽医研究所家畜疫病病原生物学国家重点实验室国家口蹄疫参考实验室,甘肃兰州730046

出　　处：《中国兽医科学》2021年第9期1134-1139,共6页Chinese Veterinary Science

基　　金：国家自然科学基金面上项目(31672538)。

摘　　要：口蹄疫病毒(FMDV)能够感染多种偶蹄动物,对畜牧业发展造成极大威胁。骨形成蛋白4(BMP4)是转化生长因子超家族成员之一,能够调节细胞的增殖、分化、凋亡和迁移,研究表明BMP4在肿瘤生长及侵袭迁移中发挥重要作用。DNA结合抑制分子-1(ID1)是广泛存在于哺乳动物细胞中的核转录因子负调控蛋白,在细胞生长、衰老和分化中发挥作用,与肿瘤的发生和发展密切相关。BMP4在FMDV感染过程中所起的作用仍不清楚。为了研究BMP4抑制FMDV复制的分子机制,采用蛋白免疫印迹(Western-blotting)和实时荧光定量(qRT-PCR)研究BMP4、ID1与FMDV之间的关系。利用FMDV感染BHK-21细胞,发现病毒感染后BMP4的m RNA和蛋白水平均有所上调,表明BMP4可能参与FMDV复制的调控。外源鼠BMP4重组蛋白刺激试验表明,BMP4可抑制FMDV的复制,并且与宿主ID1的表达呈正相关。为了验证BMP4是否通过ID1抑制FMDV的复制,利用ID1基因敲除细胞系进行感染试验,发现在ID1正常表达的细胞系中,BMP4可抑制FMDV的复制。而在ID1基因敲除细胞系中,BMP4不能抑制FMDV的复制。结果表明,BMP4通过诱导ID1蛋白的上调表达从而抑制FMDV的复制。Foot-and-mouth disease virus(FMDV)can infect many cloven-hoofed animals which hindered the development of animal husbandry.Bone morphogenetic protein 4(BMP4)is a member of the transforming growth factor superfamily.It can regulate cell proliferation,differentiation,apoptosis and migration,and studies have shown that BMP4 plays an important role in tumor growth,invasion and migration.Inhibitor of DNA binding 1(ID1)is a negative regulatory protein of nuclear transcription factors widely found in mammalian cells,which plays a role in cell growth,senescence and differentiation and is closely related to the occurrence and development of tumors.To study the molecular mechanism of BMP4 inhibiting FMDV replication.Western-blotting and quantitative real-time polymerase chain reaction(q RT-PCR)were used to research the relationship between BMP4,ID1 and FMDV.The m RNA and protein levels of BMP4 were up-regulated after FMDV infection in BHK-21 cells,indicating that BMP4 probably participate in the regulation of FMDV replication.Nextly,the exogenous mouse BMP4 recombinant protein protreatment could inhibit the replication of FMDV in cells.Futhermore,to verify whether the anti-FMDV activity of BMP4 is ID1 dependently,ID1 gene knockout cell line was used.We found that BMP4 could inhibit FMDV replication in the wild type cell line,while BMP4 disable function in ID1 knockout cell line.Collectively,these results suggest that BMP4 inhibits FMDV replication by up-regulating the expression of ID1 protein.

关 键 词：口蹄疫病毒 骨形成蛋白4 DNA结合抑制分子-1 

分 类 号：S852.659.6[农业科学—基础兽医学]