Lama J, Mangasarian A, Trono D
La Jolla Institute for Allergy and Immunology Molecular Immunology Division, 10355 Science Center Drive, San Diego, California 92121, USA.
Curr Biol. 1999 Jun 17;9(12):622-31. doi: 10.1016/s0960-9822(99)80284-x.
Human immunodeficiency virus-1 (HIV-1) infection decreases the cell-surface expression of its cellular receptor, CD4, through the combined actions of Nef, Env and Vpu. Such functional convergence strongly suggests that CD4 downregulation is critical for optimal viral replication, yet the significance of this phenomenon has so far remained a puzzle.
We show that high levels of CD4 on the surface of HIV-infected cells induce a dramatic reduction in the infectivity of released virions by the sequestering of the viral envelope by CD4. CD4 is able to accumulate in viral particles while at the same time blocking incorporation of Env into the virion. Nef and Vpu, through their ability to downregulate CD4, counteract this effect.
The CD4-mediated 'envelope interference' described here probably explains the plurality of mechanisms developed by HIV to downregulate the cell-surface expression of its receptor.
人类免疫缺陷病毒1型（HIV-1）感染通过Nef、Env和Vpu的联合作用降低其细胞受体CD4的细胞表面表达。这种功能上的趋同强烈表明CD4下调对于最佳病毒复制至关重要，然而迄今为止这一现象的意义仍是一个谜。
我们发现，HIV感染细胞表面的高水平CD4通过CD4隔离病毒包膜，导致释放的病毒粒子的感染性显著降低。CD4能够在病毒颗粒中积累，同时阻止Env掺入病毒粒子。Nef和Vpu通过下调CD4的能力抵消了这种作用。
此处描述的CD4介导的“包膜干扰”可能解释了HIV为下调其受体的细胞表面表达而发展出的多种机制。
