Miyagi Eri, Andrew Amy J, Kao Sandra, Strebel Klaus
Laboratory of Molecular Microbiology, Viral Biochemistry Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892-0460, USA.
Proc Natl Acad Sci U S A. 2009 Feb 24;106(8):2868-73. doi: 10.1073/pnas.0813223106. Epub 2009 Feb 5.
HIV-1 Vpu enhances the release of virions from infected cells. Recent work identified Bst-2/CD317/tetherin as a host factor whose inhibitory activity on viral release is counteracted by Vpu. A current working model proposes that Bst-2 inhibits virus release by tethering viral particles to the cell surface. Here, we analyzed endogenous Bst-2 with respect to its effect on virus release from HeLa cells, T cells, and macrophages. We noted significant cell type-dependent variation in Bst-2 expression. Vpu caused a reduction in Bst-2 expression in transfected HeLa cells and long-term infected macrophages. However, Vpu expression did not result in cell surface down-modulation of Bst-2 or a reduction in intracellular Bst-2 expression in CEMx174 or H9 cells, yet virus replication in these cells was Vpu-responsive. Surprisingly, Bst-2 was undetectable in cell-free virions that were recovered from the surface of HeLa cells by physical shearing, suggesting that a tethering model may not explain all of the functional properties of Bst-2. Taken together we conclude that enhancement of virus release by Vpu does not, at least in CEMx174 and H9 cells, require cell surface down-modulation or intracellular depletion of Bst-2, nor does it entail exclusion of Bst-2 from viral particles.
HIV-1 Vpu可增强病毒粒子从受感染细胞的释放。最近的研究确定Bst-2/CD317/连接蛋白是一种宿主因子,其对病毒释放的抑制活性可被Vpu抵消。当前的工作模型提出,Bst-2通过将病毒颗粒连接到细胞表面来抑制病毒释放。在此,我们分析了内源性Bst-2对其从HeLa细胞、T细胞和巨噬细胞释放病毒的影响。我们注意到Bst-2表达存在显著的细胞类型依赖性差异。Vpu可导致转染的HeLa细胞和长期感染的巨噬细胞中Bst-2表达降低。然而,Vpu的表达并未导致CEMx174或H9细胞中Bst-2的细胞表面下调或细胞内Bst-2表达的降低,但这些细胞中的病毒复制对Vpu有反应。令人惊讶的是,通过物理剪切从HeLa细胞表面回收的无细胞病毒粒子中未检测到Bst-2,这表明连接模型可能无法解释Bst-2的所有功能特性。综上所述,我们得出结论,至少在CEMx174和H9细胞中,Vpu增强病毒释放并不需要Bst-2的细胞表面下调或细胞内消耗,也不需要将Bst-2排除在病毒颗粒之外。