Department of Molecular and Structural Biochemistry, North Carolina State University, Raleigh, NC 27695, USA.
J Virol. 2011 Feb;85(3):1257-66. doi: 10.1128/JVI.01864-10. Epub 2010 Nov 17.
Bafilomycin A(1) is a specific inhibitor of the vacuolar-ATPase (V-ATPase), which is responsible for pH homeostasis of the cell and for the acidification of endosomes. Bafilomycin A(1) has been commonly used as a method of inhibition of infection by viruses known or suspected to follow the path of receptor-mediated endocytosis and low-pH-mediated membrane fusion. The exact method of entry for Sindbis virus, the prototype alphavirus, remains undetermined. To further investigate the role of the V-ATPase in Sindbis virus infection, the effects of bafilomycin A(1) on the infection of BHK and insect cells by Sindbis virus were studied. Bafilomycin A(1) was found to block the expression of a virus-encoded reporter gene in both infection and transfection of BHK cells. The inhibitory effects of bafilomycin A(1) were found to be reversible. The results suggest that in BHK cells in the presence of bafilomycin A(1), virus RNA enters the cell and is translated, but replication and proper folding of the product proteins requires the function of the V-ATPase. Bafilomycin A(1) had no significant effect on the outcome of infection in insect cells.
巴佛洛霉素 A(1) 是液泡型三磷酸腺苷酶（V-ATPase）的特异性抑制剂，它负责细胞的 pH 稳态和内体的酸化。巴佛洛霉素 A(1) 通常被用作抑制已知或疑似通过受体介导的内吞作用和低 pH 介导的膜融合途径感染的病毒的方法。辛德比斯病毒（原型甲病毒）的确切进入方式仍未确定。为了进一步研究 V-ATPase 在辛德比斯病毒感染中的作用，研究了巴佛洛霉素 A(1)对辛德比斯病毒感染 BHK 和昆虫细胞的影响。发现巴佛洛霉素 A(1)可阻断 BHK 细胞感染和转染中病毒编码报告基因的表达。发现巴佛洛霉素 A(1)的抑制作用是可逆的。结果表明，在存在巴佛洛霉素 A(1)的情况下，BHK 细胞中的病毒 RNA 进入细胞并被翻译，但产物蛋白的复制和正确折叠需要 V-ATPase 的功能。巴佛洛霉素 A(1)对昆虫细胞感染的结果没有显著影响。
