数字农科院2.0

Evaluation of the contribution of hemagglutinin-neuraminidase to the endocytic entry of Newcastle Disease Virus

文献类型： 外文期刊

作者： 赵冉;;韩宗希;;李慧昕;;邵昱昊;;孙军峰;;刘胜旺

关键词： Newcastle disease virus; Hemagglutinin-neuraminidase; Endocytic entry; Endosomes; Membrane fusion

期刊名称： VIROLOGY

ISSN： 0042-6822

年卷期： 2025 年

页码：

收录情况： SCIE（2025版）

摘要： Entry of Newcastle disease virus (NDV) into target cells via caveolae-mediated endocytosis has been presented. However, the viral factors that mediate the endocytic entry and fusion in intracellular endosomes remain poorly understood. Herein, the potential contributions of HN stalk region and second receptor biding site (site II) located at the globular head region on the endocytosis of NDV and the viral-cell membrane fusion in endosomes were investigated. HN protein mutants with substitutions at positions 89 and 94 in the stalk region and at position 516 in site II were firstly constructed. We demonstrated that mutations in HN stalk region restricted its interaction with F protein and fusion promotion activity. While mutation in HN site II resulted in slightly decreased fusion promotion activity without affected the HN-F interactions. Further evaluation of receptor binding and entry capacities with HN mutant NDVs obtained by reverse genetics demonstrated that both mutations at stalk region and site II reduced the binding abilities of NDV to receptors. Interestingly, site II in HN was not responsible for the endocytic entry of NDV and subsequent viral-cell membrane fusion in endosomes. While the residues at 89 and 94 in HN stalk region were involved in the fusion of NDV in endosomes. Of particular note, the acidic condition was indispensable for efficiently fusion triggering of NDV within endosomes. Besides, residues at 89 and 94 in HN were conserved in different genotypes of NDVs and the endocytic entry of NDV into cells was not determined by viral virulence and genotype.

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