Bhella David, Gatherer Derek, Chaudhry Yasmin, Pink Rebecca, Goodfellow Ian G
Medical Research Council Virology Unit, Glasgow University, Church St., Glasgow G11 5JR, United Kingdom.
J Virol. 2008 Aug;82(16):8051-8. doi: 10.1128/JVI.00550-08. Epub 2008 Jun 11.
The Caliciviridae family comprises positive-sense RNA viruses of medical and veterinary significance. In humans, caliciviruses are a major cause of acute gastroenteritis, while in animals respiratory illness, conjunctivitis, stomatitis, and hemorrhagic disease are documented. Investigation of virus-host interactions is limited by a lack of culture systems for many viruses in this family. Feline calicivirus (FCV), a member of the Vesivirus genus, provides a tractable model, since it may be propagated in cell culture. Feline junctional adhesion molecule 1 (fJAM-1) was recently identified as a functional receptor for FCV. We have analyzed the structure of this virus-receptor complex by cryo-electron microscopy and three-dimensional image reconstruction, combined with fitting of homology modeled high-resolution coordinates. We show that domain 1 of fJAM-1 binds to the outer face of the P2 domain of the FCV capsid protein VP1, inducing conformational changes in the viral capsid. This study provides the first structural view of a native calicivirus-protein receptor complex and insights into the mechanisms of virus attachment and uncoating.
杯状病毒科包含具有医学和兽医学意义的正链RNA病毒。在人类中,杯状病毒是急性胃肠炎的主要病因,而在动物中,有文献记载可引发呼吸道疾病、结膜炎、口腔炎和出血性疾病。由于该病毒科的许多病毒缺乏培养系统,病毒与宿主相互作用的研究受到限制。猫杯状病毒(FCV)是杯状病毒属的成员,因其可在细胞培养中繁殖,提供了一个易于处理的模型。猫连接黏附分子1(fJAM-1)最近被鉴定为FCV的功能性受体。我们通过冷冻电子显微镜和三维图像重建,结合同源建模高分辨率坐标的拟合,分析了这种病毒-受体复合物的结构。我们发现fJAM-1的结构域1与FCV衣壳蛋白VP1的P2结构域的外表面结合,诱导病毒衣壳发生构象变化。这项研究首次提供了天然杯状病毒-蛋白受体复合物的结构视图,并深入了解了病毒附着和解衣壳的机制。