Cell surface CD4 inhibits HTV-1 particle release by interfering with Vpu activity
Cell surface CD4 inhibits HTV-1 particle release by interfering with Vpu activity
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DOI：
10.1074/jbc.274.47.33800
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发表时间：
1999-11-19
影响因子：
4.8
通讯作者：
Strebel, K
中科院分区：
文献类型：
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作者：
Bour, S;Perrin, C;Strebel, K
人类免疫缺陷病毒I型（HIV-1）感染的特征之一是从细胞表面快速去除病毒受体CD4。这种非常有效的受体干扰需要三种不同的病毒蛋白的活性：Env、Vpu和Nef。我们已经研究了这种对细胞表面CD4表达的异常紧密干扰在病毒生命周期中是否具有比简单地防止重复感染更重要的功能。我们现在报道，去除细胞表面CD4是HIV-1产生最佳病毒所必需的，事实上，在感染细胞中维持CD4表面表达导致病毒颗粒产生减少3-5倍。这种作用不是由于CD4和gp160病毒包膜前体之间形成细胞内复合物，而是需要CD4在细胞表面的存在，并且是由CD4特异性介导的，而不是密切相关的质膜受体。发现CD4对Vpu缺陷变异体的颗粒释放无显著影响，表明CD4通过抑制Vpu促进颗粒释放的活性起作用。共免疫沉淀实验进一步表明，CD4和Vpu在细胞表面物理相互作用，提示CD4可能通过破坏Vpu的寡聚结构来抑制Vpu的活性。
One of the hallmarks of human immunodeficiency virus type I (HIV-1) infection is the rapid removal of the viral receptor CD4 from the cell surface. This remarkably efficient receptor interference requires the activity of three separate viral proteins: Env, Vpu, and Nef. We have investigated whether this unusually tight interference on cell surface CD4 expression had a more essential function during the viral life cycle than simply preventing superinfection. We now report that the removal of cell surface CD4 is required for optimal virus production by HIV-1, Indeed, maintenance of CD4 surface expression in infected cells lead to a 3-5-fold decrease in viral particle production. This effect was not due to the formation of intracellular complexes between CD4 and the gp160 viral envelope precursor but instead required the presence of CD4 at the cell surface and was specifically mediated by CD4 but not closely related plasma membrane receptors. The finding that CD4 had no significant effect on particle release by a Vpu-deficient variant indicates that CD4 acts by inhibiting the particle release-promoting activity of Vpu. Co-immunoprecipitation experiments further showed that CD4 and Vpu physically interact at the cell surface, suggesting that CD4 might inhibit Vpu activity by disrupting its oligomeric structure.