Garcia J V, Miller A D
Program in molecular Medicine, Fred Hutchinson Cancer Research Center, Seattle, Washington 98104.
Nature. 1991 Apr 11;350(6318):508-11. doi: 10.1038/350508a0.
A decline in the T-cell population usually marks the onset of progressive immunological disease in individuals infected with the human immunodeficiency virus (HIV). Because CD4+ cells help to coordinate efficient immune responses, some of the defects in the immune function in advanced cases of AIDS may be explained by the disappearance of these cells. Therefore, an understanding of the mechanisms used by HIV to induce the reduction of CD4+ cells is important. Here we use a Moloney murine leukaemia virus-based retroviral vector in order to express the nef gene of HIV-1 in three lymphocytic cell lines expressing CD4. In all cases we find that cell-surface CD4 expression is inversely related to nef expression. However, nef does not alter steady-state levels of CD4 RNA or CD4 protein. Also, nef can downregulate a CD4 triple mutant (Ser----Ala) that is neither phosphorylated nor down-regulated by phorbol esters, indicating that nef is acting by a different mechanism.
T细胞数量的减少通常标志着感染人类免疫缺陷病毒（HIV）的个体中进行性免疫疾病的开始。由于CD4 +细胞有助于协调有效的免疫反应，艾滋病晚期免疫功能的一些缺陷可能可以用这些细胞的消失来解释。因此，了解HIV用于诱导CD4 +细胞减少的机制很重要。在这里，我们使用基于莫洛尼鼠白血病病毒的逆转录病毒载体，以便在三种表达CD4的淋巴细胞系中表达HIV-1的nef基因。在所有情况下，我们发现细胞表面CD4表达与nef表达呈负相关。然而，nef不会改变CD4 RNA或CD4蛋白的稳态水平。此外，nef可以下调一种CD4三重突变体（Ser----Ala），该突变体既不被佛波酯磷酸化也不被其下调，这表明nef通过不同的机制起作用。
