Requirement of cholesterol in the viral envelope for dengue virus infection
Requirement of cholesterol in the viral envelope for dengue virus infection
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DOI：
10.1016/j.virusres.2013.03.005
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发表时间：
2013-06-01
期刊：
影响因子：
5
通讯作者：
Damonte, Elsa B.
中科院分区：
文献类型：
--
作者：
Carro, Ana C.;Damonte, Elsa B.
用甲基- β -环糊精（MCD）或制霉菌素（nystatin）去除病毒包膜或细胞膜中胆固醇的作用来检测登革热病毒（DENV）感染。用MCD或制霉菌素预处理病毒粒子，以剂量依赖的方式显著降低病毒的感染性。相比之下，用MCD或制霉菌素预处理多种人类细胞系对DENV感染没有影响。四种DENV血清型同样被胆固醇提取药物灭活，当病毒粒子悬浮液在牛血清存在下用MCD处理时，传染性部分恢复。MCD治疗后添加血清或外源性水溶性胆固醇并不能逆转MCD灭活作用。此外，用额外的胆固醇治疗病毒粒子也发挥了抗病毒作用。缺乏胆固醇的DENV与宿主细胞的结合和摄取并未受到损害，然而，MCD灭活的DENV病毒粒子感染的细胞中衣壳蛋白的保留，似乎阻止了病毒粒子包膜和内小体膜融合的下一步，导致病毒粒子脱包并向细胞质释放核衣壳。此后，由于mcd处理的病毒粒子感染的细胞中病毒RNA合成和病毒蛋白表达失败，感染几乎完全被抑制。这些数据表明，包膜胆固醇在DENV进入的融合过程中是一个关键因素。(C) 2013 Elsevier B.V.版权所有
The role of cholesterol in the virus envelope or in the cellular membranes for dengue virus (DENV) infection was examined by depletion with methyl-beta-cyclodextrin (MCD) or nystatin. Pretreatment of virions with MCD or nystatin significantly reduced virus infectivity in a dose-dependent manner. By contrast, pre-treatment of diverse human cell lines with MCD or nystatin did not affect DENV infection. The four DENV serotypes were similarly inactivated by cholesterol-extracting drugs and infectivity was partially rescued when virion suspensions were treated with MCD in the presence of bovine serum. The addition of serum or exogenous water-soluble cholesterol after MCD treatment did not produce a reversion of MCD inactivating effect. Furthermore, virion treatment with extra cholesterol exerted also a virucidal effect. Binding and uptake of cholesterol-deficient DENV into the host cell were not impaired, whereas the next step of fusion between virion envelope and endosome membrane leading to virion uncoating and release of nucleocapsids to the cytoplasm appeared to be prevented, as determined by the retention of capsid protein in cells infected with MCD inactivated-DENV virions. Thereafter, the infection was almost completely inhibited, given the failure of viral RNA synthesis and viral protein expression in cells infected with MCD-treated virions. These data suggest that envelope cholesterol is a critical factor in the fusion process for DENV entry. (C) 2013 Elsevier B.V. All rights reserved.