Anti-tetherin activities in Vpu-expressing primate lentiviruses.
Anti-tetherin activities in Vpu-expressing primate lentiviruses.
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DOI：
10.1186/1742-4690-7-13
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发表时间：
2010-02-18
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：
Yang SJ;Lopez LA;Hauser H;Exline CM;Haworth KG;Cannon PM
细胞限制因子BST-2/tetherin的抗病毒活性首先被观察到能够阻断Vpu-负HIV-1从感染细胞表面释放。然而，不表达Vpu蛋白的灵长类慢病毒也抵消了拴系蛋白限制，其中抗拴系蛋白功能由Env蛋白（HIV-2，SIVtan）或Nef蛋白（SIVsm/mac和SIVagm）提供。在灵长类慢病毒中，Vpu也存在于SIVcpz和某些SIVsyk病毒的基因组中。我们想知道，在这些病毒中，抗栓蛋白活性是否总是Vpu的一种特性，或者它是否在HIV-1中选择性进化以执行此功能。我们发现，尽管HIV-1和SIVcpz密切相关，但黑猩猩病毒使用Nef而不是Vpu来抵消tetherin。此外，SIVcpz Nef蛋白对黑猩猩具有活性，但对人的拴蛋白没有活性。这种特异性映射到存在于灵长类动物而非人类系链蛋白的细胞质尾区中的短序列，这也解释了SIVsm/mac Nef对灵长类动物而非人类系链蛋白的特异性。相比之下，来自SIVsyk谱系的四个不同成员的Vpu蛋白都显示出对猕猴拴系蛋白有活性的抗拴系蛋白活性。有趣的是，来自SIVgsn分离物的Vpu也被发现具有针对人拴蛋白的活性。灵长类慢病毒在其使用抗栓蛋白因子方面显示出高度的灵活性，表明对抗栓蛋白限制的强选择压力。在SIVgsn Vpu中鉴定出针对人系链蛋白的活性表明，在被认为贡献了HIV-1基因组的3'半的祖先SIVmus/mon/gsn病毒中Vpu的存在可能在能够对抗人系链蛋白并感染人类的病毒的进化中发挥了作用。
The anti-viral activity of the cellular restriction factor, BST-2/tetherin, was first observed as an ability to block the release of Vpu-minus HIV-1 from the surface of infected cells. However, tetherin restriction is also counteracted by primate lentiviruses that do not express a Vpu protein, where anti-tetherin functions are provided by either the Env protein (HIV-2, SIVtan) or the Nef protein (SIVsm/mac and SIVagm). Within the primate lentiviruses, Vpu is also present in the genomes of SIVcpz and certain SIVsyk viruses. We asked whether, in these viruses, anti-tetherin activity was always a property of Vpu, or if it had selectively evolved in HIV-1 to perform this function. We found that despite the close relatedness of HIV-1 and SIVcpz, the chimpanzee viruses use Nef instead of Vpu to counteract tetherin. Furthermore, SIVcpz Nef proteins had activity against chimpanzee but not human tetherin. This specificity mapped to a short sequence that is present in the cytoplasmic tail of primate but not human tetherins, and this also accounts for the specificity of SIVsm/mac Nef for primate but not human tetherins. In contrast, Vpu proteins from four diverse members of the SIVsyk lineage all displayed an anti-tetherin activity that was active against macaque tetherin. Interestingly, Vpu from a SIVgsn isolate was also found to have activity against human tetherin. Primate lentiviruses show a high degree of flexibility in their use of anti-tetherin factors, indicating a strong selective pressure to counteract tetherin restriction. The identification of an activity against human tetherin in SIVgsn Vpu suggests that the presence of Vpu in the ancestral SIVmus/mon/gsn virus believed to have contributed the 3' half of the HIV-1 genome may have played a role in the evolution of viruses that could counteract human tetherin and infect humans.
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影响因子：
5.4
作者：
HIRSCH, VM;DAPOLITO, GA;JOHNSON, PR
通讯作者：
JOHNSON, PR
影响因子：
30.3
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6.7
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McNatt, Matthew W.;Zang, Trinity;Hatziioannou, Theodora;Bartlett, Mackenzie;Ben Fofana, Ismael;Johnson, Welkin E.;Neil, Stuart J. D.;Bieniasz, Paul D.
通讯作者：
Bieniasz, Paul D.
影响因子：
6.7
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Gupta RK;Hué S;Schaller T;Verschoor E;Pillay D;Towers GJ
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Towers GJ