Cloning and characterization of the antiviral activity of feline Tetherin/BST-2.
Cloning and characterization of the antiviral activity of feline Tetherin/BST-2.
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DOI：
10.1371/journal.pone.0018247
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发表时间：
2011-03-29
期刊：
影响因子：
3.7
通讯作者：
Yasuda J
中科院分区：
文献类型：
--
作者：
Fukuma A;Abe M;Morikawa Y;Miyazawa T;Yasuda J
Human Tetherin/BST-2 最近被确定为一种细胞抗病毒因子，可以阻止各种包膜病毒的释放。在这项研究中，我们克隆了编码 Tetherin/BST-2 猫科动物同源物的 cDNA 片段，并表征了蛋白质产物。人Tetherin/BST-2与猫科动物同源物之间的氨基酸序列同一性程度为44.4%。与人 Tetherin/BST-2 类似，猫 Tetherin/BST-2 mRNA 的表达可由 I 型干扰素 (IFN) 诱导。猫 Tetherin/BST-2 的外源表达有效抑制猫内源性逆转录病毒 RD-114 的释放。猫科动物 Tetherin/BST-2 的胞外结构域有两个假定的 N 连接糖基化位点：N79 和 N119。通过在两个位点引入突变，N-连接糖基化完全丧失，导致其抗病毒活性几乎完全丧失。此外，猫Tetherin/BST-2对HIV-1 Vpu的拮抗作用不敏感，尽管人Tetherin/BST-2的抗病毒活性被HIV-1 Vpu拮抗。我们的数据表明，猫科动物 Tetherin/BST-2 是 IFN 诱导的针对病毒感染的先天免疫的一部分，并且体内诱导猫科动物 Tetherin/BST-2 可能作为一种有效的新型抗病毒策略来治疗病毒感染。
Human Tetherin/BST-2 has recently been identified as a cellular antiviral factor that blocks the release of various enveloped viruses. In this study, we cloned a cDNA fragment encoding a feline homolog of Tetherin/BST-2 and characterized the protein product. The degree of amino acid sequence identity between human Tetherin/BST-2 and the feline homolog was 44.4%. Similar to human Tetherin/BST-2, the expression of feline Tetherin/BST-2 mRNA was inducible by type I interferon (IFN). Exogenous expression of feline Tetherin/BST-2 efficiently inhibited the release of feline endogenous retrovirus RD-114. The extracellular domain of feline Tetherin/BST-2 has two putative N-linked glycosylation sites, N79 and N119. Complete loss of N-linked glycosylation by introduction of mutations into both sites resulted in almost complete abolition of its antiviral activity. In addition, feline Tetherin/BST-2 was insensitive to antagonism by HIV-1 Vpu, although the antiviral activity of human Tetherin/BST-2 was antagonized by HIV-1 Vpu. Our data suggest that feline Tetherin/BST-2 functions as a part of IFN-induced innate immunity against virus infection and that the induction of feline Tetherin/BST-2 in vivo may be effective as a novel antiviral strategy for viral infection.