Endocytosis of chikungunya virus into mammalian cells: role of clathrin and early endosomal compartments.
Endocytosis of chikungunya virus into mammalian cells: role of clathrin and early endosomal compartments.
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DOI：
10.1371/journal.pone.0011479
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发表时间：
2010-07-08
期刊：
影响因子：
3.7
通讯作者：
Briant L
中科院分区：
文献类型：
--
作者：
Bernard E;Solignat M;Gay B;Chazal N;Higgs S;Devaux C;Briant L
基孔肯雅病毒(CHIKV)是一种最近在印度和印度洋地区重新出现的甲型病毒，其复制周期大多尚不清楚。本研究的目的是研究CHIKV劫持进入哺乳动物细胞的细胞内转运途径(S)。使用多种药理抑制剂或过度表达干扰细胞内吞作用的显性阴性形式的蛋白质来研究进入途径。我们发现CHIKV对HEK293T哺乳动物细胞的感染不依赖于笼蛋白重链，并依赖于功能上的Eps15，并且需要Rab5-而不是Rab7阳性的内体隔室的完整性。细胞骨架的完整性是至关重要的，因为细胞松弛素D和诺康唑显着减少了细胞的感染。最后，甲基β-环糊精和促溶体药物都能损伤CHIKV感染，支持需要依赖胆固醇和pH的步骤才能实现生产性感染。有趣的是，在从留尼汪岛最近暴发的LR-OPY1病毒中分离出的37997非洲株CHIKV和LR-OPY1病毒之间观察到对溶体增殖剂的不同敏感性。总而言之，我们的数据表明CHIKV进入其靶细胞基本上是通过依赖于笼蛋白的、依赖于Eps15的内吞作用来调节的。尽管从留尼汪岛最近的暴发中分离出的37997非洲新城疫病毒的原型毒株和LR-OPY1病毒具有这种特性，但对溶体促进剂的不同敏感性可能支持LR-OPY1毒株获得了特定的进入机制。
The replicative cycle of chikungunya virus (CHIKV), an alphavirus that recently re-emerged in India and in Indian Ocean area, remains mostly unknown. The aim of the present study was to investigate the intracellular trafficking pathway(s) hijacked by CHIKV to enter mammalian cells. Entry pathways were investigated using a variety of pharmacological inhibitors or overexpression of dominant negative forms of proteins perturbating cellular endocytosis. We found that CHIKV infection of HEK293T mammalian cells is independent of clathrin heavy chain and- dependent of functional Eps15, and requires integrity of Rab5-, but not Rab7-positive endosomal compartment. Cytoskeleton integrity is crucial as cytochalasin D and nocodazole significantly reduced infection of the cells. Finally, both methyl β-cyclodextrin and lysomotropic agents impaired CHIKV infection, supporting that a cholesterol-, pH-dependent step is required to achieve productive infection. Interestingly, differential sensitivity to lysomotropic agents was observed between the prototypal 37997 African strain of CHIKV and the LR-OPY1 virus isolated from the recent outbreak in Reunion Island. Together our data indicate that CHIKV entry in its target cells is essentially mediated by clathrin-independent, Eps15-dependent endocytosis. Despite that this property is shared by the prototypal 37997 African strain of CHIKV and the LR-OPY1 virus isolated from the recent outbreak in La Réunion Island, differential sensitivity to lysomotropic agents may support that the LR-OPY1 strain has acquired specific entry mechanisms.
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影响因子：
3.8
作者：
GRAHAM, FL;SMILEY, J;NAIRN, R
通讯作者：
NAIRN, R
DOI：
10.1016/j.trstmh.2004.03.013
发表时间：
2005-02-01
影响因子：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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