Jin Y M, Churchill N D, Michalak T I
Division of Basic Medical Sciences, Faculty of Medicine, Health Sciences Centre, Memorial University of Newfoundland, St John's, Canada.
J Gen Virol. 1996 Aug;77 ( Pt 8):1837-46. doi: 10.1099/0022-1317-77-8-1837.
A site capable of strictly host- and cell type-specific recognition was identified in the preS1 domain of woodchuck hepatitis virus (WHV) through the use of antipeptide antisera generated against the extreme N-terminal fragment of the large virus envelope protein. The crucial determinant of this binding site was mapped to amino acids 10-13. Although a synthetic analogue of the site was highly immunogenic, natural WHV envelope did not display the site activity unless it was modified by proteolysis or acidic pH treatment, indicating an internal location of the determinant in viral envelope. Synthetic peptides encompassing the sequence of this site bound woodchuck lymphoid cells and hepatocytes in a species-restricted manner which followed characteristics of a specific ligand-receptor interaction, although their ability to interact with lymphoid cells was considerably greater than that for hepatocytes. In WHV-infected animals, a natural antibody to the identified cryptic cell-binding site arose independently of that directed against epitopes of unmodified virus envelope and its appearance constituted the earliest immunovirological indicator of virus invasion. Our results demonstrated that the preS1 domain of the large WHV envelope protein is endowed with the species- and cell type-specific recognition site which is protected against antibody surveillance by the natural tertiary structure of the protein and we suggest that proteolytic cleavage is required to induce the binding activity.
通过使用针对大型病毒包膜蛋白极端N端片段产生的抗肽抗血清，在土拨鼠肝炎病毒（WHV）的前S1结构域中鉴定出一个能够严格进行宿主和细胞类型特异性识别的位点。该结合位点的关键决定因素被定位到第10 - 13位氨基酸。尽管该位点的合成类似物具有高度免疫原性，但天然WHV包膜除非经过蛋白水解或酸性pH处理，否则不会显示出该位点活性，这表明决定因素在病毒包膜内部。包含该位点序列的合成肽以物种限制的方式结合土拨鼠淋巴细胞和肝细胞，遵循特定配体 - 受体相互作用的特征，尽管它们与淋巴细胞相互作用的能力比与肝细胞的相互作用能力大得多。在感染WHV的动物中，针对已鉴定的隐蔽细胞结合位点的天然抗体独立于针对未修饰病毒包膜表位的抗体而产生，其出现构成了病毒入侵的最早免疫病毒学指标。我们的结果表明，大型WHV包膜蛋白的前S1结构域具有物种和细胞类型特异性识别位点，该位点受到蛋白质天然三级结构的保护，免受抗体监测，并且我们认为需要蛋白水解切割来诱导结合活性。
