López-Guerrero J A, Cabañas C, Bernabeu C, Fresno M, Alonso M A
Centro de Biología Molecular, Universidad Autónoma CSIC, Madrid, Spain.
Virus Res. 1989 Sep;14(1):65-72. doi: 10.1016/0168-1702(89)90070-1.
Monocytic U937 cells can differentiate in vitro into macrophage-like cells by treatment with phorbol esters such as phorbol 12-myristate 13-acetate (PMA). We have analyzed the effect of poliovirus infection in this pathway of differentiation. Poliovirus RNA replication took place in both untreated and PMA-treated U937 cells infected before or after PMA addition, although a slight reduction in poliovirus RNA levels was observed in PMA-treated cells at late times postinfection. Total protein synthesis remained unchanged during the first 5 h of infection both in normal and PMA-treated cells. However, an inhibition on total RNA synthesis was observed early in infection. PMA-induced c-myc mRNA expression was abolished when infection took place 1 h before PMA addition but was just partially inhibited when poliovirus was added 1 h after PMA stimulation. Fluorescence flow cytometry analysis revealed that poliovirus infection induced an increase in the number of 4F2 molecules per cell in normal U937 cells and a slight decrease in the number of positive cells for the antigens CD14, CD4 and CD11c in both untreated or PMA-treated U937 cells. These findings suggest that poliovirus infection of U937 cells interferes at various levels with monocyte maturation yielding cells which are unable to undergo the complete pathway of differentiation to macrophages.
单核细胞系U937细胞可通过用佛波酯如佛波醇12 -肉豆蔻酸酯13 -乙酸酯(PMA)处理,在体外分化为巨噬细胞样细胞。我们分析了脊髓灰质炎病毒感染在这条分化途径中的作用。脊髓灰质炎病毒RNA复制在添加PMA之前或之后感染的未处理和PMA处理的U937细胞中均会发生,尽管在感染后期PMA处理的细胞中观察到脊髓灰质炎病毒RNA水平略有降低。在感染的前5小时,正常细胞和PMA处理的细胞中总蛋白质合成均保持不变。然而,在感染早期观察到总RNA合成受到抑制。当在添加PMA前1小时发生感染时,PMA诱导的c - myc mRNA表达被消除,但当在PMA刺激后1小时添加脊髓灰质炎病毒时,其仅被部分抑制。荧光流式细胞术分析显示,脊髓灰质炎病毒感染导致正常U937细胞中每个细胞的4F2分子数量增加,并且在未处理或PMA处理的U937细胞中,抗原CD14、CD4和CD11c的阳性细胞数量略有减少。这些发现表明,U937细胞的脊髓灰质炎病毒感染在多个水平上干扰单核细胞成熟,产生无法经历向巨噬细胞完全分化途径的细胞。