Stehle T, Yan Y, Benjamin T L, Harrison S C
Howard Hughes Medical Institute, Harvard University, Cambridge, Massachusetts 02138.
Nature. 1994 May 12;369(6476):160-3. doi: 10.1038/369160a0.
The polyomaviruses are non-enveloped, icosahedrally symmetrical particles with circular double-stranded DNA genomes. The outer shell of the virion contains 360 copies of viral protein VP1 (M(r) approximately 42K) arranged in pentamers. We report here the structure at 3.65 A resolution of murine polyomavirus ('polyoma') complexed with an oligosaccharide receptor fragment. This structure has been determined using the previously described model of simian virus 40 (SV40). Although very similar in structure to SV40, polyoma has interesting biological differences. Cell-surface N-acetyl neuraminic acid (sialic acid) is required for polyoma infectivity, but not for SV40. Polyoma attaches to the surface of susceptible cells by stereospecific recognition of oligosaccharides terminating in (alpha 2,3)-linked sialic acid. Studies of pathogenicity show that the specificity of viral binding to such oligosaccharides is an important determinant of the virus' ability to establish a disseminated infection and to induce tumours in the natural host. The complex described here show how polyoma recognizes the receptor fragment and how strains with different receptor specificities can distinguish between alternative ligands. The results also suggest an explanation for the large disparity in pathogenicity exhibited by strains differing in only one amino-acid residue of VP1.
多瘤病毒是无包膜的、具有二十面体对称结构的颗粒，其基因组为环状双链DNA。病毒粒子的外壳包含360个以五聚体形式排列的病毒蛋白VP1（相对分子质量约为42K）拷贝。我们在此报告了与寡糖受体片段复合的小鼠多瘤病毒（“多瘤病毒”）在3.65埃分辨率下的结构。该结构是使用先前描述的猴病毒40（SV40）模型确定的。尽管多瘤病毒在结构上与SV40非常相似，但它具有有趣的生物学差异。多瘤病毒感染需要细胞表面的N - 乙酰神经氨酸（唾液酸），而SV40则不需要。多瘤病毒通过立体特异性识别以（α2,3）连接的唾液酸结尾的寡糖附着在易感细胞表面。致病性研究表明，病毒与此类寡糖结合的特异性是病毒在天然宿主中建立播散性感染并诱导肿瘤能力的重要决定因素。这里描述的复合物展示了多瘤病毒如何识别受体片段以及具有不同受体特异性的毒株如何区分不同的配体。结果还为仅在VP1的一个氨基酸残基上不同的毒株所表现出的致病性巨大差异提供了解释。
