Department of Infectious Diseases, Virology, University of Heidelberg, Im Neuenheimer Feld 324, D-69120 Heidelberg, Germany.
J Virol. 2010 Apr;84(8):4089-94. doi: 10.1128/JVI.01549-09. Epub 2010 Feb 10.
Vpu antagonizes human immunodeficiency virus type 1 (HIV-1) particle release inhibition by CD317/BST-2/Tetherin. Whether this Vpu activity strictly requires cellular depletion of the restriction factor is unclear. Here, we characterized CD317 variants with mutations in putative sorting or ubiquitination motifs. All mutants still potently impaired release of Vpu-defective HIV-1 and remained sensitive to Vpu-mediated release enhancement. Importantly, this virological antagonism correlated with surface downregulation of CD317 mutants by Vpu, while intracellular pools of these mutants, which were consistently depleted of the wild-type protein, were highly variable or even enhanced. Thus, Vpu can efficiently antagonize virion tethering in the absence of CD317 degradation.
Vpu 拮抗人免疫缺陷病毒 1 型（HIV-1）颗粒释放抑制物 CD317/BST-2/Tetherin。Vpu 的这种活性是否严格依赖于细胞内限制因子的耗竭尚不清楚。在这里，我们对具有假定分选或泛素化基序突变的 CD317 变体进行了表征。所有突变体仍能强烈抑制 Vpu 缺陷型 HIV-1 的释放，并且仍然对 Vpu 介导的释放增强敏感。重要的是，这种病毒学拮抗作用与 Vpu 介导的 CD317 突变体表面下调相关，而这些突变体的细胞内池，其野生型蛋白始终被耗尽，高度可变，甚至增强。因此，Vpu 可以在不降解 CD317 的情况下有效地拮抗病毒的 tethering。
