MONENSIN INHIBITS SEMLIKI FOREST VIRUS PENETRATION INTO CULTURE CELLS
MONENSIN INHIBITS SEMLIKI FOREST VIRUS PENETRATION INTO CULTURE CELLS
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DOI：
10.1073/pnas.79.17.5297
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
HELENIUS, A
中科院分区：
文献类型：
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作者：
MARSH, M;WELLSTEED, J;HELENIUS, A
浓度分别为10微克和6微克的羧基离子载体莫能菌素和黑素可阻止塞姆利基森林病毒(SFV)基因组穿透幼鼠肾(BHK-21)细胞的胞浆，从而抑制病毒复制。在没有抑制剂的情况下，已知SFV的进入是通过包被小泡的吸附内吞作用进行的，随后是酸引发的细胞内空泡或溶酶体的膜融合。病毒与细胞表面的结合、吸附内吞作用和细胞内病毒向溶酶体的运输仅受到离子载体的轻微影响。没有观察到直接杀灭病毒的作用，也没有直接影响病毒在低pH下的膜融合活性。顺序加入莫能菌素和NH4Cl(一种与SFV进入无关的溶酶体亲和性抑制剂)表明，这两种抑制剂影响进入途径的同一步骤。根据这些数据和已知的羧基离子载体和溶酶体弱碱对细胞pH梯度的影响，莫能菌素明显地通过增加细胞内空泡和溶酶体的pH来抑制穿透，pH 6是病毒膜融合活性的pH阈值。
The carboxylic ionophores monensin and nigericin, at concentrations > 10 and 6 .mu.M, respectively, prevent the penetration of the Semliki Forest virus (SFV) genome into the cytosol of baby hamster kidney (BHK-21) cells and thereby inhibit viral replication. In the absence of inhibitors, the entry of SFV is known to proceed by adsorptive endocytosis in coated vesicles, followed by acid-triggered membrane fusion in intracellular vacuoles or lysosomes. Binding of the virus to the cell surface, adsorptive endocytosis and intracellular transport of viruses to the lysosomes are only marginally affected by the ionophores. No direct virucidal effect is observed, nor is the membrane fusion activity of the virus at low pH directly affected. Sequential addition of monensin and NH4Cl (a nonrelated lysosomotropic inhibitor of SFV entry) indicates that both inhibitors affect the same step in the entry pathway. On the basis of these data and the known effects of carboxylic ionophores and lysosomotropic weak bases on cellular pH gradients, monensin evidently inhibits penetration by increasing the pH in endocytic vacuoles and lysosomes above pH 6, which is the pH threshold for the viral membrane fusion activity.