Gangliosides are receptors for murine polyoma virus and SV40
Gangliosides are receptors for murine polyoma virus and SV40
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DOI：
10.1093/emboj/cdg439
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发表时间：
2003-09-01
期刊：
影响因子：
11.4
通讯作者：
Rapoport, TA
中科院分区：
文献类型：
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作者：
Tsai, B;Gilbert, JM;Rapoport, TA
多瘤病毒（Py）和猿猴病毒40 （SV40）从质膜传播到内质网（ER），从内质网进入细胞质，然后进入细胞核开始感染。在这里，我们证明了特定的神经节苷脂可以作为这些病毒的质膜受体，GD1a和GT1b用于Py， GM1用于SV40。结合和浮选试验表明，将这些神经节苷脂添加到磷脂囊泡中可以特异性结合各自的病毒。利用含有唾液酸的寡糖的多瘤VP1的晶体结构，推导出GD1a和GT1b分支中的两个末端糖（唾液酸- α 2,3-半乳糖）如何被病毒识别的模型。缺乏神经节苷脂合成的大鼠细胞系对多瘤和SV40的感染性较差，但添加适当的神经节苷脂极大地促进了病毒的摄取、转运到内质网和感染。多瘤的脂质结合位点显示存在于粗糙的内质网膜中，这表明病毒与神经节苷脂一起从质膜进入内质网。
Polyoma virus (Py) and simian virus 40 (SV40) travel from the plasma membrane to the endoplasmic reticulum (ER) from where they enter the cytosol and then the nucleus to initiate infection. Here we demonstrate that specific gangliosides can serve as plasma membrane receptors for these viruses, GD1a and GT1b for Py and GM1 for SV40. Binding and flotation assays were used to show that addition of these gangliosides to phospholipid vesicles allowed specific binding of the respective viruses. The crystal structure of polyoma VP1 with a sialic acid-containing oligosaccharide was used to derive a model of how the two terminal sugars (sialic acid-alpha2,3-galactose) in one branch of GD1a and GT1b are recognized by the virus. A rat cell line deficient in ganglioside synthesis is poorly infectible by polyoma and SV40, but addition of the appropriate gangliosides greatly facilitates virus uptake, transport to the ER and infection. Lipid binding sites for polyoma are shown to be present in rough ER membranes, suggesting that the virus travel with the ganglioside(s) from the plasma membranes to the ER.