Association of heat-shock protein 70 with lipid rafts is required for Japanese encephalitis virus infection in Huh7 cells.
Association of heat-shock protein 70 with lipid rafts is required for Japanese encephalitis virus infection in Huh7 cells.
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Huh7 细胞中的日本脑炎病毒感染需要热激蛋白 70 与脂筏的关联。
DOI：
10.1099/vir.0.034637-0
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Ming-Mei Cao
中科院分区：
文献类型：
--
作者：
Zhong-Tian Qi;Ping Zhao;Wen Wang;Yong-Zhe Zhu;Hao Ren;Wen-Bo Wang;Ming-Mei Cao
日本脑炎病毒（Japanese encephalitis virus，JEV）是一种有包膜的黄病毒，是病毒性脑炎最常见的病原体.它通过受体介导的内吞作用和低pH触发的膜融合进入细胞。虽然脂筏，富含胆固醇的脂质有序的膜结构域，已被证明参与JEV进入，JEV感染的早期事件的机制，包括JEV的细胞受体，仍然在很大程度上是未知的。在目前的研究中，它表明，热休克蛋白70（HSP 70），而不是HSP 70家族的其他成员，需要JEV进入人类细胞系。观察到HSP 70在细胞表面的表达以及JEV包膜（E）蛋白与HSP 70之间的直接相互作用。生化分级显示，HSP 70明显迁移到筏级分病毒感染后，与E蛋白共分级。胆固醇的消耗将E蛋白和HSP 70转移到非筏膜，并减少JEV进入而不影响病毒与宿主细胞的结合。值得注意的是，在JEV感染的早期阶段，需要将HSP 70募集到脂筏中以激活磷酸肌醇3-激酶/Akt信号通路。这些结果表明，脂筏促进JEV进入，可能是通过提供一个方便的平台，集中JEV及其受体的宿主细胞膜上。
Japanese encephalitis virus (JEV) is an enveloped flavivirus and the most common agent of viral encephalitis. It enters cells through receptor-mediated endocytosis and low pH-triggered membrane fusion. Although lipid rafts, cholesterol-enriched lipid-ordered membrane domains, have been shown to participate in JEV entry, the mechanisms of the early events of JEV infection, including the cellular receptors of JEV, remain largely unknown. In the current study, it was demonstrated that heat-shock protein 70 (HSP70), rather than other members of the HSP70 family, was required for JEV entry into a human cell line. Cell-surface expression of HSP70 and a direct interaction between JEV envelope (E) protein and HSP70 were observed. Biochemical fractionation showed that HSP70 clearly migrated into the raft fraction after virus infection and co-fractioned with E protein. Depletion of cholesterol shifted the E protein and HSP70 to a non-raft membrane and decreased JEV entry without affecting virus binding to host cells. Notably, recruitment of HSP70 into lipid rafts was required for activation of the phosphoinositide 3-kinase/Akt signalling pathway in the early stage of JEV infection. These results indicate that lipid rafts facilitate JEV entry, possibly by providing a convenient platform to concentrate JEV and its receptors on the host-cell membrane.
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作者：
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影响因子：
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作者：
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