Chi Miaomiao, Liu Ying, Wen Hongling, Zhao Li, Song Yanyan, Liu Na, Chi Lianli, Wang Zhiyu
Department of Virology, School of Public Health, Shandong University, Jinan 250012, PR China.
State Key Laboratory of Microbial Technology, National Glycoengineering Research Center, Shandong University, Jinan 250100, PR China.
J Gen Virol. 2020 Jan;101(1):5-20. doi: 10.1099/jgv.0.001349.
To gain insights into the role of the head-stalk linker region in the fusion triggering, we constructed mutants by deleting or substituting the linker region (115-NGAANNSG-122) of Newcastle disease virus (NDV) haemagglutinin-neuraminidase (HN) with the corresponding sequences of other paramyxoviruses. The results showed that these HN mutants exhibited different levels of fusion-triggering activity, but most of them maintained comparable levels with wide-type HN in both receptor recognition and neuraminidase activity. We tried to figure out reasons for fusion alteration through assessing the expression and the oligomeric state of HN mutants. Moreover, four mutants with significant fusion changes were introduced into the headless HN stem (HN1-123) to intensively investigate the role of the linker region in fusion triggering. Consequently, the stability of HN oligomers and the structural integrity of the 4 helical-bundle of stalk have complicated influences on the alteration of fusion-triggering activities for different mutants. These data suggested that the head-stalk linker could regulate the fusion triggering at both full-length and headless HN levels.
为深入了解头柄连接区在融合触发中的作用,我们构建了突变体,通过用其他副粘病毒的相应序列删除或替换新城疫病毒(NDV)血凝素神经氨酸酶(HN)的连接区(115-NGAANNSG-122)。结果表明,这些HN突变体表现出不同水平的融合触发活性,但它们中的大多数在受体识别和神经氨酸酶活性方面与野生型HN保持相当的水平。我们试图通过评估HN突变体的表达和寡聚状态来找出融合改变的原因。此外,将四个融合变化显著的突变体引入无头HN茎(HN1-123),以深入研究连接区在融合触发中的作用。因此,HN寡聚体的稳定性和柄部4螺旋束的结构完整性对不同突变体融合触发活性的改变具有复杂的影响。这些数据表明,头柄连接区可以在全长和无头HN水平上调节融合触发。