Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo.

Swine interferon-induced transmembrane protein, sIFITM3, inhibits foot-and-mouth disease virus infection in vitro and in vivo.
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猪干扰素诱导的跨膜蛋白sIFITM3在体外和体内抑制口蹄疫病毒感染

DOI:
10.1016/j.antiviral.2014.06.008
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发表时间:
2014-09
期刊:
影响因子:
7.6
通讯作者:
Li X
Li X
中科院分区:
医学2区
文献类型:
--
作者:
Xu J;Qian P;Wu Q;Liu S;Fan W;Zhang K;Wang R;Zhang H;Chen H;Li X

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猪IFITM 3(sIFITM 3)与其人类直系同源物共享保守的功能结构域和氨基酸残基。sIFITM 3在BHK细胞中限制FMDV感染。sIFITM 3破坏FMDV病毒与宿主细胞表面的附着。sIFITM 3保护乳鼠免受FMDV攻击。干扰素诱导的跨膜蛋白3(IFITM 3)是宿主先天免疫系统中广泛表达的有效抗病毒效应物。它通过干扰内体融合来限制不同种类的致病性包膜病毒。本研究克隆了猪IFITM 3(sIFITM 3)基因。它与其人类直系同源物共享功能上保守的CD 225结构域和多个关键氨基酸残基(Y19、F74、F77、R86和Y 98),这对于抗病毒活性是必需的。sIFITM 3的异位表达显著抑制无包膜口蹄疫病毒(FMDV)在BHK-21细胞中的感染。此外,sIFITM 3通过破坏病毒与宿主细胞表面的附着,在病毒生命周期的早期阶段阻断FMDV感染。重要的是,用表达sIFITM 3的质粒接种2日龄乳鼠,可保护其免受FMDV致死性攻击。这些结果表明,sIFITM 3是一种有前途的抗病毒剂,可以保护宿主免受FMDV感染。
Swine IFITM3 (sIFITM3) shares the conserved functional domains and amino acid residues with its human ortholog. sIFITM3 restricts FMDV infection in BHK cells. sIFITM3 disrupts FMDV viral attachment to the host cell surface. sIFITM3 protects suckling mice from FMDV challenge. The interferon-induced transmembrane protein 3 (IFITM3) is a widely expressed potent antiviral effector of the host innate immune system. It restricts a diverse group of pathogenic, enveloped viruses, by interfering with endosomal fusion. In this report, the swine IFITM3 (sIFITM3) gene was cloned. It shares the functionally conserved CD225 domain and multiple critical amino acid residues (Y19, F74, F77, R86 and Y98) with its human ortholog, which are essential for antiviral activity. Ectopic expression of sIFITM3 significantly inhibited non-enveloped foot-and-mouth disease virus (FMDV) infection in BHK-21 cells. Furthermore, sIFITM3 blocked FMDV infection at early steps in the virus life cycle by disrupting viral attachment to the host cell surface. Importantly, inoculation of 2-day-old suckling mice with a plasmid expressing sIFITM3 conferred protection against lethal challenge with FMDV. These results suggest that sIFITM3 is a promising antiviral agent and that can safeguard the host from infection with FMDV.
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