Mutated form of the Newcastle disease virus hemagglutinin-neuraminidase interacts with the homologous fusion protein despite deficiencies in both receptor recognition and fusion promotion
Mutated form of the Newcastle disease virus hemagglutinin-neuraminidase interacts with the homologous fusion protein despite deficiencies in both receptor recognition and fusion promotion
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DOI：
10.1128/jvi.78.10.5299-5310.2004
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发表时间：
2004-05-01
影响因子：
5.4
通讯作者：
Iorio, RM
中科院分区：
文献类型：
--
作者：
Li, JR;Quinlan, E;Iorio, RM
纽卡斯尔病病毒（NDV）血凝素-神经氨酸酶（HN）蛋白介导与细胞受体的附着。融合（F）蛋白促进病毒进入和传播。然而，融合依赖于两种蛋白质之间的病毒特异性相互作用，其可以通过免疫共沉淀测定在细胞表面检测到。神经氨酸酶（NA）活性位点中I175 E的点突变将澳大利亚-维多利亚分离株病毒的HN转化为可与F蛋白相互作用的形式，尽管受体识别和融合促进活性可忽略不计。因此，I175 E-HN可以代表融合中间体，其中HN和F相关联并引发促进融合。该突变HN蛋白的附着和融合促进活性可以通过另一HN蛋白贡献的NA活性或通过二聚体界面处的一组四个取代来拯救。通过评价由来自两种不同NDV毒株的HN蛋白片段组成的嵌合体来鉴定这些置换。这些发现表明I175 E取代将HN转化为F-相互作用形式，但它仍然是促进融合所需的受体结合形式。数据还表明HN二聚体界面的完整性对其受体识别活性至关重要。
The Newcastle disease virus (NDV) hemagglutinin-neuraminidase (HN) protein mediates attachment to cellular receptors. The fusion (F) protein promotes viral entry and spread. However, fusion is dependent on a virus-specific interaction between the two proteins that can be detected at the cell surface by a coimmunoprecipitation assay. A point mutation of I175E in the neuraminidase (NA) active site converts the HN of the Australia-Victoria isolate of the virus to a form that can interact with the F protein despite negligible receptor recognition and fusion-promoting activities. Thus, I175E-HN could represent a fusion intermediate in which HN and F are associated and primed for the promotion of fusion. Both the attachment and fusion-promoting activities of this mutant HN protein can be rescued either by NA activity contributed by another HN protein or by a set of four substitutions at the dimer interface. These substitutions were identified by the evaluation of chimeras composed of segments from HN proteins derived from two different NDV strains. These findings suggest that the I175E substitution converts HN to an F-interactive form, but it is one for which receptor binding is still required for fusion promotion. The data also indicate that the integrity of the HN dimer interface is critical to its receptor recognition activity.