Tobiume M, Tokunaga K, Kiyokawa E, Takahoko M, Mochizuki N, Tatsumi M, Matsuda M
Department of Pathology, Research Institute, International Medical Center of Japan, Tokyo.
Arch Virol. 2001;146(9):1739-51. doi: 10.1007/s007050170060.
The nef gene of human immunodeficiency virus type 1 (HIV-1) encodes a 27 to 34 kDa myristoylated protein, which enhances viral infectivity in a single-round infection assay. The level of Nef enhancement of HIV-1 infectivity depends on the viral strains, on the target cells, and on the cells used for propagating the viruses. In this study, we aimed at clarifying the molecular basis of these differences in the requirement for Nef. We found that the requirement for Nef was increased when we decreased the quantity of Env protein in the virus-producing cells or the quantity of CD4 in the target cells. Both the wild-type and Nef-defective HIV-1 viruses were propagated in 293T cells, which did not express any CD4; therefore, Nef-induced CD4 down-regulation did not explain this phenomenon. Moreover, we did not observe any increase in the viral entry or fusion activity of gp120env in the wild-type HIV-1 compared to that in the Nef-defective HIV-1. Thus, we propose that Env on the virion and CD4 on the target cells have inhibitory effects on the post-entry step of the HIV-1 replication cycle, and that Nef functions to counteract this negative effect.
人类免疫缺陷病毒1型（HIV-1）的nef基因编码一种27至34 kDa的肉豆蔻酰化蛋白，该蛋白在单轮感染试验中可增强病毒的感染性。HIV-1感染性的Nef增强水平取决于病毒株、靶细胞以及用于繁殖病毒的细胞。在本研究中，我们旨在阐明这些Nef需求差异的分子基础。我们发现，当我们减少病毒产生细胞中Env蛋白的量或靶细胞中CD4的量时，对Nef的需求会增加。野生型和Nef缺陷型HIV-1病毒均在不表达任何CD4的293T细胞中繁殖；因此，Nef诱导的CD4下调并不能解释这一现象。此外，与Nef缺陷型HIV-1相比，我们未观察到野生型HIV-1中gp120env的病毒进入或融合活性有任何增加。因此，我们提出病毒体上的Env和靶细胞上的CD4对HIV-1复制周期的进入后步骤具有抑制作用，而Nef的功能是抵消这种负面影响。
