Identification of amino acid residues important to the neuraminidase activity of the HN glycoprotein of Newcastle disease virus.
Identification of amino acid residues important to the neuraminidase activity of the HN glycoprotein of Newcastle disease virus.
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DOI：
10.1016/0042-6822(89)90235-3
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发表时间：
1989-11
期刊：
影响因子：
3.7
通讯作者：
R. M. Iorio;R. Syddall;R. Glickman;Anne M. Kiel;John P. Sheehan;M. A. Bratt
中科院分区：
文献类型：
--
作者：
R. M. Iorio;R. Syddall;R. Glickman;Anne M. Kiel;John P. Sheehan;M. A. Bratt
针对新城疫病毒(NDV)血凝素神经氨酸酶糖蛋白(HN)上三个重叠抗原位点(分别命名为12、2和23)的单抗(MAb)以前被证明能抑制神经氨酸乳糖上的神经氨酸酶活性(R.M.Iorio和M.A.Bratt，1984a，J.Immunol.133,2215-2219；R.M.Iorio等，1989，Virus Res.13,245-262)。然而，NA的竞争性抑制剂只阻止单抗与23位点的结合，这表明他们识别的结构域可能与NA位点密切相关。用23位单抗选择的抗原变异体在HN残基192、193或200位有单一氨基酸替换。变异体的病毒粒子在残基193或200处有替换，在NA中有变化，这不是由于HN含量的相应变化。与野生型相比，温度敏感型突变体的NA显著减少，在第175位有氨基酸替代。第二步revenant部分恢复了NA，在残基192处有一个额外的替换，与23位变异体中的一个相同，这反过来也使突变体对23位单抗的中和产生抵抗。因此，新城疫病毒HN的175、193或200位氨基酸的替换可以对蛋白质的NA产生显著的影响。在新城疫病毒和其他副粘病毒的HN之间，175位残基附近的氨基酸是高度保守的，这表明该结构域对于这组病毒NA位点的完整性是重要的。
Monoclonal antibodies (MAbs) to three overlapping antigenic sites (designated 12, 2, and 23) on the hemagglutininneuraminidase glycoprotein (HN) of Newcastle disease virus (NDV) were previously shown to inhibit neuraminidase activity (NA) on neuraminlactose (R. M. Iorio and M. A. Bratt, 1984a,J. Immunol.133, 2215–2219; R. M. Iorio et al., 1989,Virus Res.13, 245–262). However, a competitive inhibitor of NA blocks the binding of only MAbs to site 23, suggesting that the domain they recognize may be closely related to the NA site. Antigenic variants selected with site 23 MAbs have single amino acid substitutions at HN residues 192, 193, or 200. Virions of variants, which have a substitution at residue 193 or 200, have alterations in NA which are not attributable to a commensurate change in HN content. A revertant of a temperature-sensitive mutant, which has markedly diminished NA relative to the wild type, has an amino acid substitution at residue 175. A second step revenant having partially restored NA has an additional substitution at residue 192 identical to that in one of the site 23 variants, which, in turn, also makes the revertant resistant to neutralization by site 23 MAbs. Thus, an amino acid substitution at residue 175, 193, or 200 of the HN of NDV can have marked effects on the NA of the protein. The amino acids in the region around residue 175 are highly conserved between the HNs of NDV and other paramyxoviruses, suggesting that this domain is important to the integrity of the NA site in this group of viruses.