HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment.

HIV-1 Vpu and HIV-2 Env counteract BST-2/tetherin by sequestration in a perinuclear compartment.
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DOI:
10.1186/1742-4690-7-51
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发表时间:
2010-06-07
期刊:
影响因子:
3.3
通讯作者:
Cannon PM
Cannon PM
中科院分区:
医学2区
文献类型:
--
作者:
Hauser H;Lopez LA;Yang SJ;Oldenburg JE;Exline CM;Guatelli JC;Cannon PM

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在没有Vpu蛋白的情况下,由于干扰素诱导的细胞限制因子BST-2/tetherin的作用,新形成的HIV-1颗粒可以保持附着在人细胞表面。栓系蛋白还限制其他包膜病毒颗粒的释放,并被几种病毒抗栓系蛋白因子抵消,包括HIV-2 Env、SIV Nef和KSHV K5蛋白。我们观察到,一小部分的tetherin位于限制性细胞的表面,并且HIV-1 Vpu和HIV-2 Env的共表达减少了该群体。此外,Vpu(而不是HIV-2 Env)降低了细胞内拴系蛋白的总水平。对于Vpu和HIV-2 Env观察到的另一个作用是将拴蛋白重定向到与TGN(trans-Golgi网络)标记物重叠的细胞内核周区室。在这一区室中的拴系蛋白的隔离是独立的拴系蛋白的正常内吞运输途径。HIV-1 Vpu和HIV-2 Env都能使系链蛋白从细胞表面转移,并将其隔离在核周区室中,这可能会阻断这种细胞限制因子的作用。Vpu还促进了tetherin的降解,这表明它使用了不止一种机制来抵消tetherin限制。
In the absence of the Vpu protein, newly formed HIV-1 particles can remain attached to the surface of human cells due to the action of an interferon-inducible cellular restriction factor, BST-2/tetherin. Tetherin also restricts the release of other enveloped viral particles and is counteracted by a several viral anti-tetherin factors including the HIV-2 Env, SIV Nef and KSHV K5 proteins. We observed that a fraction of tetherin is located at the surface of restricting cells, and that co-expression of both HIV-1 Vpu and HIV-2 Env reduced this population. In addition, Vpu, but not the HIV-2 Env, reduced total cellular levels of tetherin. An additional effect observed for both Vpu and the HIV-2 Env was to redirect tetherin to an intracellular perinuclear compartment that overlapped with markers for the TGN (trans-Golgi network). Sequestration of tetherin in this compartment was independent of tetherin's normal endocytosis trafficking pathway. Both HIV-1 Vpu and HIV-2 Env redirect tetherin away from the cell surface and sequester the protein in a perinuclear compartment, which likely blocks the action of this cellular restriction factor. Vpu also promotes the degradation of tetherin, suggesting that it uses more than one mechanism to counteract tetherin restriction.
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