Virulence of Newcastle diseasevirus is determined by the cleavage site of the fusion protein and by both the stem region and globular head of the haemagglutinin-neuraminidase protein
Virulence of Newcastle diseasevirus is determined by the cleavage site of the fusion protein and by both the stem region and globular head of the haemagglutinin-neuraminidase protein
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DOI：
10.1099/vir.0.80822-0
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发表时间：
2005-06-01
影响因子：
3.8
通讯作者：
Peeters, BPH
中科院分区：
文献类型：
--
作者：
de Leeuw, OS;Koch, G;Peeters, BPH
新城疫病毒（NDV）的毒力主要由融合（F）蛋白切割位点周围的氨基酸序列决定，因为切割强毒株F蛋白的宿主蛋白酶比切割无毒株F蛋白的宿主蛋白酶存在于更多的组织中。然而，对携带完全相同的F蛋白裂解位点的NDV毒株进行比较表明，毒力仍然存在显着差异。例如，具有 F 裂解位点 (112)RRQRRF(117) 的强毒野菌株 Herts/33 的脑内致病性指数为 1.88，而具有相同裂解位点的菌株 NDFLtag 的脑内致病性指数为 1.28。这意味着其他因素会导致毒力。在生成 Herts/33 (FL-Herts) 的感染性克隆后，我们能够通过在 FL-Herts 和 NDFLtag 之间交换序列来绘制其他毒力因子的位置。结果表明，除了F蛋白裂解位点外，血凝素神经氨酸酶（HN）蛋白也对毒力有贡献。 HN蛋白对毒力的影响在静脉接种后最为显着。有趣的是，HN 蛋白的茎区和球状头似乎都参与毒力的决定。
Virulence of Newcastle disease virus (NDV) is mainly determined by the amino acid sequence surrounding the fusion (F) protein cleavage site, since host proteases that cleave the F protein of virulent strains are present in more tissues than those that cleave the F protein of non-virulent strains. Nevertheless, comparison of NDV strains that carry exactly the same F protein cleavage site shows that significant differences in virulence still exist. For instance, virulent field strain Herts/33 with the F cleavage site (112)RRQRRF(117) had an intracerebral pathogenicity index of 1.88 compared with 1.28 for strain NDFLtag, which has the same cleavage site. This implies that additional factors contribute to virulence. After generating an infectious clone of Herts/33 (FL-Herts), we were able to map the location of additional virulence factors by exchanging sequences between FL-Herts and NDFLtag. The results showed that, in addition to the F protein cleavage site, the haemagglutinin-neuraminidase (HN) protein also contributed to virulence. The effect of the HN protein on virulence was most prominent after intravenous inoculation. Interestingly, both the stem region and the globular head of the HN protein seem to be involved in determining virulence.