Evidence for Paralichthys olivaceus IFITM1 antiviral effect by impeding viral entry into target cells.

Evidence for Paralichthys olivaceus IFITM1 antiviral effect by impeding viral entry into target cells.
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牙鲆 IFITM1 通过阻止病毒进入靶细胞而发挥抗病毒作用的证据

DOI:
10.1016/j.fsi.2013.07.002
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发表时间:
2013-09
影响因子:
4.7
通讯作者:
Zhang QY
Zhang QY
中科院分区:
农林科学2区
文献类型:
--
作者:
Zhu R;Wang J;Lei XY;Gui JF;Zhang QY

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干扰素诱导跨膜蛋白家族是一类具有典型跨膜结构的新型病毒限制因子。这些蛋白质也存在于鱼类中,但它们在先天免疫反应中的作用尚不清楚。在这里,我们报道了牙鲆硬骨IFITM1(PoIFITM1)的特征,它具有IFITM家族的保守结构特征,但包含一个相对较长的N-末端区域。PoIFITM1的表达和启动子活性明显受水生动物病毒--林蛙病毒(Rana grylio Virus,RGV)和大菱角扇贝病毒(Scophthalmus Larus RhabdoVirus,SMRV)诱导。过表达和siRNA介导的敲除表明,PoIFITM1对DNA病毒(RGV)和RNA病毒(SMRV)都有很强的抗病毒作用,扩大了IFITM蛋白抑制病毒的范围。进一步的分析表明,PoIFITM1抑制病毒进入宿主细胞,证实了IFITM介导的限制从低等脊椎动物到哺乳动物是保守的。缺失突变表明,PoIFITM1通过靶向高尔基复合体发挥抗病毒活性,其N-末端区域是其亚细胞定位所必需的,这在其他已知的IFITM家族成员中没有观察到。我们目前的数据提供了第一个证据,表明IFITM1作为先天免疫的关键效应器,通过阻止病毒进入的作用来限制低等脊椎动物的病毒复制。牙鲆IFITM1基因的首次克隆及其功能研究。PoIFITM1由两种水生动物病毒引起:RGV和SMRV。PoIFITM1对DNA和RNA病毒都有很强的抗病毒作用。PoIFITM1抑制病毒进入鱼类细胞。N末端通过调节细胞定位来决定其抗病毒活性。
Interferon-inducible transmembrane (IFITM) protein family is novel viral restriction factors with representative transmembrane structure. These proteins also exist in fish, however, their roles in the innate immune response remain unknown. Here, we report a characterization of teleost IFITM1 from flounder Paralichthys olivaceus (PoIFITM1), which exhibits conserved structure characteristic of the IFITM family but comprises a relatively longer N-terminal region. The expression and promoter activity of PoIFITM1 are markedly induced by aquatic animal viruses: Rana grylio virus (RGV) and Scophthalmus maximus rhabdovirus (SMRV). Overexpression and siRNA-mediated knockdown demonstrate that PoIFITM1 exhibits strong antiviral effects against both DNA virus (RGV) and RNA virus (SMRV), expanding the spectrum of viruses inhibited by IFITM proteins. Further analysis shows that PoIFITM1 suppresses viral entry into host cells, confirming that the IFITM-mediated restriction is conserved from lower vertebrates to mammals. Deletion mutagenesis reveals that PoIFITM1 exerts antiviral activity by targeting to Golgi complex and the N-terminal region is required for its subcellular localization, which is not observed in other known IFITM family members. Our current data provide the first evidence that IFITM1 functions as a key effector of the innate immune to restrict virus replication in lower vertebrates, through the action of impeding viral entry. First cloning and functional characterization of IFITM1 in flounder Paralichthys olivaceus. PoIFITM1 is induced by two aquatic animal viruses: RGV and SMRV. PoIFITM1 exhibits strong antiviral effects against both DNA and RNA viruses. PoIFITM1 suppresses viral entry into fish cells. The N-terminus determines the antiviral activity through regulating the cellular localization.
DOI: 10.3354/dao060241
发表时间: 2004-09-08
影响因子: 1.4
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DOI: 10.1128/jvi.78.15.7938-7944.2004
发表时间: 2004-08-01
影响因子: 5.4
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DOI: 10.1038/nature10921
发表时间: 2012-03-25
期刊: NATURE
影响因子: 64.8
作者:
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