Equine Tetherin Blocks Retrovirus Release and Its Activity Is Antagonized by Equine Infectious Anemia Virus Envelope Protein
Equine Tetherin Blocks Retrovirus Release and Its Activity Is Antagonized by Equine Infectious Anemia Virus Envelope Protein
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DOI：
10.1128/jvi.03148-13
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发表时间：
2013-11
影响因子：
5.4
通讯作者：
Xin Yin;Zhe Hu;Qinyong Gu;Xingliang Wu;Yong-Hui Zheng;P. Wei;Xiaojun Wang
中科院分区：
文献类型：
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作者：
Xin Yin;Zhe Hu;Qinyong Gu;Xingliang Wu;Yong-Hui Zheng;P. Wei;Xiaojun Wang
人链蛋白是一种宿主限制因子，通过阻断病毒释放来抑制包膜病毒的复制。Tetherin具有不寻常的拓扑结构，包括n端细胞质尾部，单个跨膜结构域，细胞外结构域和c端糖基磷脂酰肌醇锚定。Tetherin在物种间并不是很保守，因此它以物种特异性的方式抑制病毒复制。因此，研究不同物种的tetherin活性为了解其抗病毒机制提供了重要工具。在这里，我们报道克隆马绳蛋白和表征其抗病毒活性。马拴链蛋白与猫、人、猿和鼠拴链蛋白的氨基酸序列同源性分别为53%、40%、36%和34%。和猫科动物的系绳蛋白一样，马的系绳蛋白的n端结构域比人类的短。马tetherin定位于细胞表面，并强烈阻止人类免疫缺陷病毒1型（HIV-1）、猴免疫缺陷病毒（SIV）和马传染性贫血病毒（EIAV）从病毒产生细胞释放。马系绳素的抗病毒活性可被EIAV包膜蛋白中和，但不能被HIV-1辅助蛋白Vpu中和，Vpu是人系绳素拮抗剂，EIAV包膜蛋白不能中和人系绳素。这些结果为我们对物种特异性tetherin抗病毒机制的理解提供了新的线索。
ABSTRACT Human tetherin is a host restriction factor that inhibits replication of enveloped viruses by blocking viral release. Tetherin has an unusual topology that includes an N-terminal cytoplasmic tail, a single transmembrane domain, an extracellular domain, and a C-terminal glycosylphosphatidylinositol anchor. Tetherin is not well conserved across species, so it inhibits viral replication in a species-specific manner. Thus, studies of tetherin activities from different species provide an important tool for understanding its antiviral mechanism. Here, we report cloning of equine tetherin and characterization of its antiviral activity. Equine tetherin shares 53%, 40%, 36%, and 34% amino acid sequence identity with feline, human, simian, and murine tetherins, respectively. Like the feline tetherin, equine tetherin has a shorter N-terminal domain than human tetherin. Equine tetherin is localized on the cell surface and strongly blocks human immunodeficiency virus type 1 (HIV-1), simian immunodeficiency virus (SIV), and equine infectious anemia virus (EIAV) release from virus-producing cells. The antiviral activity of equine tetherin is neutralized by EIAV envelope protein, but not by the HIV-1 accessory protein Vpu, which is a human tetherin antagonist, and EIAV envelope protein does not counteract human tetherin. These results shed new light on our understanding of the species-specific tetherin antiviral mechanism.