Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin–neuraminidase (HN) glycoprotein

Chicken galectin-1B inhibits Newcastle disease virus adsorption and replication through binding to hemagglutinin–neuraminidase (HN) glycoprotein
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鸡半乳糖凝集素-1B 通过与血凝素神经氨酸酶 (HN) 糖蛋白结合抑制新城疫病毒吸附和复制

DOI:
10.1074/jbc.m116.772897
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发表时间:
2017-10
影响因子:
4.8
通讯作者:
Shengwang Liu
Shengwang Liu
中科院分区:
生物学2区
文献类型:
--
作者:
Junfeng Sun;Zongxi Han;Tianming Qi;Ran Zhao;Shengwang Liu

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Galectin-1是一种重要的免疫调节因子,可通过结合病毒表面的糖链介导宿主与病原体的相互作用,包括弱原性纽卡斯尔病病毒(NDV)在内的禽呼吸道病毒均可诱导鸡Galectin-1B在主要靶器官表达上调。本研究探讨了CG-1B是否参与了NDV对鸡的感染过程。本研究证实了强毒NDV可诱导CG-1B在靶器官中表达上调,CG-1B可直接与NDV病毒颗粒结合,并抑制其血凝活性。我们证实CG-1B与NDV血凝素-神经氨酸酶(HN)糖蛋白相互作用,其中特异性的G4 N-聚糖对CG-1B与HN糖蛋白的相互作用有显著贡献。细胞外CG-1B的存在,而不是内化过程,抑制NDV的吸附。在NDV感染的DF-1细胞中,细胞内CG-1B和NDV HN糖蛋白之间的相互作用抑制HN糖蛋白的细胞表面表达,并降低子代病毒的滴度。值得注意的是,亲本和HN糖基化突变体病毒在CG-1B敲低和过表达细胞中的复制表明,NDV的复制与CG-1B的表达以特定的聚糖依赖性方式相关。总之,我们的结果表明CG-1B通过结合HN糖蛋白上的N-聚糖而具有抗NDV活性。
Galectin-1 is an important immunoregulatory factor and can mediate the host–pathogen interaction via binding glycans on the surface of various viruses.Wepreviously reported that avian respiratory viruses, including lentogenic Newcastle disease virus (NDV), can induce up-regulation of chicken galectin (CG)-1B in the primary target organ. In this study, we investigated whether CG-1B participated in the infectious process of NDV in chickens. We demonstrated that velogenic NDV induced up-regulation of CG-1B in target organs.Wealso found that CG-1B directly bound to NDV virions and inhibited their hemagglutination activity in vitro. We confirmed that CG-1B interacted with NDV hemagglutinin–neuraminidase (HN) glycoprotein, in which the specific G4 N-glycans significantly contributed to the interaction between CG-1B and HN glycoprotein. The presence of extracellular CG-1B, rather than the internalization process, inhibited adsorption of NDV. The interaction between intracellular CG-1B and NDV HN glycoproteins inhibited cell-surface expression of HN glycoprotein and reduced the titer of progeny virus in NDV-infected DF-1 cells. Significantly, the replication of parental and HN glycosylation mutant viruses in CG-1B knockdown and overexpression cells demonstrated that the replication of NDV was correlated with the expression of CG-1B in a specific glycan-dependent manner. Collectively, our results indicate that CG-1B has anti-NDV activity by binding to N-glycans on HN glycoprotein.
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