Department of Virology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, 250014, China.
Jinan Central Hospital, Cheeloo College of Medicine, Shandong University, Jinan, 250014, China.
J Microbiol. 2021 May;59(5):513-521. doi: 10.1007/s12275-021-0539-4. Epub 2021 Mar 29.
Newcastle disease, designated a class A disease of poultry by the Office international des epizooties (OIE), is an acute infection caused by Newcastle disease virus (NDV). The merging of the envelope of NDV with the membrane of a target host cell is the key step in the infection pathway, which is driven by the concerted action of two glycoproteins: haemagglutinin-neuraminidase (HN) and fusion (F) protein. When the HN protein binds to the host cell surface receptor, the F protein is activated to mediate fusion. The three-dimensional structure of the F protein has been reported to have low electron density between the DIII domain and the HRB domain, and this electron-poor region is defined as the HRB linker. To clarify the contributing role of the HRB linker in the NDV F protein-mediated fusion process, 6 single amino acid mutants were obtained by site-directed mutagenesis of the HRB linker. The expression of the mutants and their abilities to mediate fusion were analysed, and the key amino acids in the HRB linker were identified as L436, E439, I450, and S453, as they can modulate the fusion ability or expression of the active form to a certain extent. The data shed light on the crucial role of the F protein HRB linker in the acquisition of a normal fusogenic phenotype.
新城疫是由国际动物卫生组织（OIE）指定的 A 类家禽疾病，是由新城疫病毒（NDV）引起的急性感染。NDV 包膜与靶宿主细胞膜融合是感染途径的关键步骤，这是由两种糖蛋白的协同作用驱动的：血凝素-神经氨酸酶（HN）和融合（F）蛋白。当 HN 蛋白与宿主细胞表面受体结合时，F 蛋白被激活以介导融合。已经报道 F 蛋白的三维结构在 DIII 结构域和 HRB 结构域之间具有低电子密度，这个电子贫乏区域被定义为 HRB 连接子。为了阐明 HRB 连接子在 NDV F 蛋白介导的融合过程中的贡献作用，通过 HRB 连接子的定点突变获得了 6 种单氨基酸突变体。分析了突变体的表达及其介导融合的能力，并鉴定出 HRB 连接子中的关键氨基酸为 L436、E439、I450 和 S453，因为它们可以在一定程度上调节融合能力或活性形式的表达。这些数据揭示了 F 蛋白 HRB 连接子在获得正常融合表型中的关键作用。
