BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol
BAP31 and BiP are essential for dislocation of SV40 from the endoplasmic reticulum to the cytosol
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DOI：
10.1038/ncb2339
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发表时间：
2011-11-01
影响因子：
21.3
通讯作者：
Helenius, Ari
中科院分区：
文献类型：
--
作者：
Geiger, Roger;Andritschke, Daniel;Helenius, Ari
无包膜病毒如何克服宿主细胞膜知之甚少。在这里，我们表明，内吞作用和运输到内质网（ER）后，但在穿过ER膜的胞质溶胶，传入的猿猴病毒40颗粒的结构重塑导致暴露的氨基末端序列的次要病毒蛋白VP 2。这些疏水序列将病毒锚在细胞膜上。α-螺旋膜包埋肽中的带负电荷的残基Glu 17是感染所必需的，最有可能是通过引入膜蛋白的ER相关降解（ERAD）系统识别的“不规则性”。使用siRNA介导的筛选，内腔伴侣BiP和ER膜蛋白BAP 31（均参与ERAD）被鉴定为感染所必需的。它们与病毒共定位在离散的病灶中，并促进其ER到胞质溶胶的移位。缺乏VP 2的病毒样颗粒未能穿过膜。结果表明，ERAD因子有助于病毒转运穿过ER膜。
How non-enveloped viruses overcome host cell membranes is poorly understood. Here, we show that after endocytosis and transport to the endoplasmic reticulum (ER), but before crossing the ER membrane to the cytosol, incoming simian virus 40 particles are structurally remodelled leading to exposure of the amino-terminal sequence of the minor viral protein VP2. These hydrophobic sequences anchor the virus to membranes. A negatively charged residue, Glu 17, in the alpha-helical, membrane-embedded peptide is essential for infection, most likely by introducing an 'irregularity' recognized by the ER-associated degradation (ERAD) system for membrane proteins. Using a siRNA-mediated screen, the lumenal chaperone BiP and the ER-membrane protein BAP31 (both involved in ERAD) were identified as being essential for infection. they co-localized with the virus in discrete foci and promoted its ER-to-cytosol dislocation. Virus-like particles devoid of VP2 failed to cross the membrane. The results demonstrated that ERAD-factors assist virus transport across the ER membrane.