The Pirbright Institute, Guildford, Surrey, GU24 0NF, UK.
MRC University of Glasgow Centre for Virus Research, Glasgow, UK.
J Gen Virol. 2021 Apr;102(4). doi: 10.1099/jgv.0.001580.
The enveloped morbilliviruses utilise conserved proteinaceous receptors to enter host cells: SLAMF1 or Nectin-4. Receptor binding is initiated by the viral attachment protein Haemagglutinin (H), with the viral Fusion protein (F) driving membrane fusion. Crystal structures of the prototypic morbillivirus measles virus H with either SLAMF1 or Nectin-4 are available and have served as the basis for improved understanding of this interaction. However, whether these interactions remain conserved throughout the morbillivirus genus requires further characterisation. Using a random mutagenesis approach, based on error-prone PCR, we targeted the putative receptor binding site for SLAMF1 interaction on peste des petits ruminants virus (PPRV) H, identifying mutations that inhibited virus-induced cell-cell fusion. These data, combined with structural modelling of the PPRV H and ovine SLAMF1 interaction, indicate this region is functionally conserved across all morbilliviruses. Error-prone PCR provides a powerful tool for functionally characterising functional domains within viral proteins.
SLAMF1 或 Nectin-4。受体结合由病毒附着蛋白血凝素 (H) 启动，病毒融合蛋白 (F) 驱动膜融合。麻疹病毒 H 与 SLAMF1 或 Nectin-4 的原型副黏病毒的晶体结构可用，并为更好地理解这种相互作用提供了依据。然而，这种相互作用是否在整个副黏病毒属中仍然保守，需要进一步的特征描述。我们使用易错 PCR 为基础的随机诱变方法，针对小反刍兽疫病毒 (PPRV) H 上与 SLAMF1 相互作用的假定受体结合位点，鉴定出抑制病毒诱导的细胞融合的突变。这些数据，结合 PPRV H 和绵羊 SLAMF1 相互作用的结构建模，表明该区域在所有副黏病毒中具有功能保守性。易错 PCR 为功能表征病毒蛋白内的功能域提供了一种强大的工具。
