Tsai Billy, Gilbert Joanna M, Stehle Thilo, Lencer Wayne, Benjamin Thomas L, Rapoport Tom A
Howard Hughes Medical Institute and Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA.
EMBO J. 2003 Sep 1;22(17):4346-55. doi: 10.1093/emboj/cdg439.
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.
多瘤病毒(Py)和猴病毒40(SV40)从质膜进入内质网(ER),并从内质网进入胞质溶胶,然后进入细胞核以引发感染。在这里,我们证明特定的神经节苷脂可作为这些病毒的质膜受体,Py的受体为GD1a和GT1b,SV40的受体为GM1。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使各自的病毒发生特异性结合。利用多瘤病毒VP1与含唾液酸的寡糖的晶体结构,建立了一个模型,以说明GD1a和GT1b一个分支中的两个末端糖(唾液酸-α2,3-半乳糖)是如何被病毒识别的。缺乏神经节苷脂合成的大鼠细胞系对多瘤病毒和SV40的感染性较差,但添加适当的神经节苷脂可极大地促进病毒摄取、转运至内质网并引发感染。多瘤病毒的脂质结合位点存在于粗面内质网膜中,这表明病毒与神经节苷脂一起从质膜转运至内质网。