Vpu-mediated tetherin antagonism of ongoing HIV-1 infection in CD4+ T-cells is not directly related to the extent of tetherin cell surface downmodulation

Vpu-mediated tetherin antagonism of ongoing HIV-1 infection in CD4+ T-cells is not directly related to the extent of tetherin cell surface downmodulation
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DOI:
10.1016/j.virol.2011.06.012
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发表时间:
2011-09-01
期刊:
影响因子:
3.7
通讯作者:
Wainberg, Mark A.
Wainberg, Mark A.
中科院分区:
医学3区
文献类型:
--
作者:
Kuhl, Bjoern D.;Sloan, Richard D.;Wainberg, Mark A.

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Tetherin是一种宿主细胞限制因子,对HIV-1和其他包膜病毒起作用。tetherin的抗病毒活性被HIV-1蛋白Vpu拮抗,Vpu从细胞表面下调tetherin。在这里,我们报告了在原代活化的CD4(+) t细胞和CD4(+) t细胞系中特异性检测细胞表面栓素水平。在tetherin细胞表面表达、vpu介导的tetherin下调和促进病毒释放方面观察到差异。然而,Vpu在所有t细胞系中的表达导致3天后感染细胞数量增加2倍。这意味着vpu介导的作用在持续感染中,可能在细胞间病毒传播中独立于vpu介导的tetherin细胞表面下调的程度。感染vpu缺失病毒后,t细胞系中内源性细胞表面tetherin水平也下调,这表明HIV-1感染后t细胞系中tetherin细胞表面下调的另一种不依赖vpu的机制。(C) 2011爱思唯尔公司版权所有。
Tetherin is a host cell restriction factor that acts against HIV-1 and other enveloped viruses. The antiviral activity of tetherin is antagonized by the HIV-1 protein Vpu, that downregulates tetherin from the cell surface. Here, we report the specific detection of cell surface tetherin levels in primary activated CD4(+) T-cells and in CD4(+) T-cell lines. Differences were observed regarding tetherin cell surface expression, Vpu-mediated tetherin downmodulation and promotion of virus release. However, Vpu expression in all T-cell lines resulted in a 2-fold increase in numbers of infected cells after three days. This implies a Vpu-mediated effect in ongoing infection and possibly in cell-to-cell viral spread that is independent of the extent of Vpu-mediated tetherin cell surface downmodulation. Endogenous cell surface tetherin levels in T-cell lines were also down-modulated following infection with Vpu-deleted virus, suggesting an additional Vpu-independent mechanism of tetherin cell surface downmodulation following HIV-1 infection in T-cell lines. (C) 2011 Elsevier Inc. All rights reserved.