Determinants in HIV-2 Env and tetherin required for functional interaction.
Determinants in HIV-2 Env and tetherin required for functional interaction.
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DOI：
10.1186/s12977-015-0194-0
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发表时间：
2015-08-07
期刊：
影响因子：
3.3
通讯作者：
Cannon PM
中科院分区：
文献类型：
--
作者：
Exline CM;Yang SJ;Haworth KG;Rengarajan S;Lopez LA;Droniou ME;Seclen E;Cannon PM
干扰素诱导因子BST-2/tetherin阻断某些包膜病毒家族从感染细胞表面释放新生病毒粒子。灵长类慢病毒已经进化出几种对抗机制，在HIV-2的情况下，这是其Env蛋白的功能。我们试图进一步了解Env蛋白和tetherin的特征，这些特征对这种相互作用很重要，并评估HIV-2维持这种活性的选择性压力。通过检查Env突变体，其蛋白质的胞外域（病毒ROD 14）或胞质尾区（取代Y 707 A）发生变化，使得蛋白质不能抵消栓系蛋白，我们确定Env和栓系蛋白之间的相互作用对于该活性是重要的。此外，这种Env-连接蛋白相互作用需要连接蛋白胞外域中的丙氨酸面，尽管将该结构域插入人工连接蛋白样蛋白不足以赋予对HIV-2 Env的敏感性。携带ROD 14取代的病毒的复制明显慢于匹配的野生型病毒，但它在Env的胞质尾中传代期间获得了第二位点突变，这恢复了蛋白质结合和抵消系链蛋白的能力。这些结果揭示了HIV-2和拴系蛋白之间的相互作用，表明映射到两种蛋白质的胞外域的物理相互作用，并表明在HIV-2 Env中维持抗拴系蛋白活性的强烈选择压力。
The interferon-inducible factor BST-2/tetherin blocks the release of nascent virions from the surface of infected cells for certain enveloped virus families. The primate lentiviruses have evolved several counteracting mechanisms which, in the case of HIV-2, is a function of its Env protein. We sought to further understand the features of the Env protein and tetherin that are important for this interaction, and to evaluate the selective pressure on HIV-2 to maintain such an activity. By examining Env mutants with changes in the ectodomain of the protein (virus ROD14) or the cytoplasmic tail (substitution Y707A) that render the proteins unable to counteract tetherin, we determined that an interaction between Env and tetherin is important for this activity. Furthermore, this Env-tetherin interaction required an alanine face in the tetherin ectodomain, although insertion of this domain into an artificial tetherin-like protein was not sufficient to confer sensitivity to the HIV-2 Env. The replication of virus carrying the ROD14 substitutions was significantly slower than the matched wild-type virus, but it acquired second-site mutations during passaging in the cytoplasmic tail of Env which restored the ability of the protein to both bind to and counteract tetherin. These results shed light on the interaction between HIV-2 and tetherin, suggesting a physical interaction that maps to the ectodomains of both proteins and indicating a strong selection pressure to maintain an anti-tetherin activity in the HIV-2 Env.