Institute of Biochemistry, ETH Zurich, Schafmattstrasse 18, CH-8093 Zurich, Switzerland.
Nat Cell Biol. 2011 Sep 25;13(11):1305-14. doi: 10.1038/ncb2339.
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 α-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.
包膜病毒如何克服宿主细胞膜尚不清楚。在这里，我们表明，在进入细胞内体并运输到内质网 (ER) 之后，但在穿过 ER 膜进入细胞质之前，进入的猿猴病毒 40 颗粒会发生结构重塑，导致次要病毒蛋白 VP2 的氨基末端序列暴露。这些疏水性序列将病毒锚定在膜上。在螺旋、膜嵌入肽中的带负电荷的残基 Glu17 对于感染是必需的，这很可能是通过引入 ER 相关降解 (ERAD) 系统识别的“不规则性”来实现的，该系统是用于膜蛋白的。通过 siRNA 介导的筛选，发现腔衬钙结合蛋白 BiP 和 ER 膜蛋白 BAP31（均参与 ERAD）对于感染是必需的。它们与病毒在离散焦点中共定位，并促进其从 ER 到细胞质的易位。缺乏 VP2 的病毒样颗粒无法穿过膜。结果表明，ERAD 因子有助于病毒穿过 ER 膜的运输。
