FUNCTIONAL AND NEUTRALIZATION PROFILE OF 7 OVERLAPPING ANTIGENIC SITES ON THE HN GLYCOPROTEIN OF NEWCASTLE-DISEASE VIRUS - MONOCLONAL-ANTIBODIES TO SOME SITES PREVENT VIRAL ATTACHMENT
FUNCTIONAL AND NEUTRALIZATION PROFILE OF 7 OVERLAPPING ANTIGENIC SITES ON THE HN GLYCOPROTEIN OF NEWCASTLE-DISEASE VIRUS - MONOCLONAL-ANTIBODIES TO SOME SITES PREVENT VIRAL ATTACHMENT
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DOI：
10.1016/0168-1702(89)90019-1
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发表时间：
1989-07-01
期刊：
影响因子：
5
通讯作者：
BRATT, MA
中科院分区：
文献类型：
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作者：
IORIO, RM;GLICKMAN, RL;BRATT, MA
我们以前已经在新城疫病毒澳大利亚-维多利亚分离株(Iorio和Bratt，J.Virol)的血凝素神经氨酸酶(HN)糖蛋白上鉴定了五个抗原位点。48,440-450；Iorio等人，J.Gen.Virol。67、1393-1403)。现在描述了另外两个位点(指定为12和23)，使我们的中和抗HN抗体小组定义的抗原位点总数达到7个。竞争抗体结合和加性中和分析表明，这些新鉴定的位点中的每一个都与先前定义的两个重叠。因此，这七个HN抗原点在分子的三维构象中形成了一个连续体。对血凝(HA)、神经氨酸酶(NA)的抑制和病毒与鸡细胞单层的附着的研究已经被用来构建每个抗原点的功能图谱。抗三个重叠部位(12、2和23)的单抗可抑制HA和NA，并阻止病毒附着在鸡细胞单层上。这些发现与这些单抗识别的结构域接近NA和受体结合位点是一致的。与另外两个重叠位点14和1的单抗(这两个重叠位点依次与重叠位点12重叠)对HA的抑制作用相当有效，并且附着程度较小。第14位和第1位可能识别与受体识别有关的第二个结构域。剩下的两个位点(3和4)的单抗虽然是中和的，但在所有三种检测中都是阴性的，因此识别不涉及HA或NA或与鸡细胞附着的区域。
We have previously identified five antigenic sites on the hemagglutinin-neuraminidase (HN) glycoprotein of the Australia-Victoria isolate of Newcastle disease virus (Iorio and Bratt, J. Virol. 48, 440-450; Iorio et al., J. Gen. Virol. 67, 1393-1403). Two additional sites (designated 12 and 23) are now described, bringing to a total of seven the number of antigenic sites defined by our panel of neutralizing anti-HN antibodies. Competition antibody binding and additive neutralization assays reveal that each of these newly-identified sites overlaps two previously-defined ones. The seven HN antigenic sites thus form a continuum in the three-dimensional conformation of the molecule. Studies on the inhibition of hemagglutination (HA), neuraminidase (NA) and the attachment of virus to chick cell monolayers have been used to construct a functional profile of each antigenic site. Monoclonal antibodies (mAbs) to three overlapping sites (12, 2 and 23) inhibit HA and NA and prevent viral attachment ot chick cell monolayers. These findings are consistent with the domains recognized by these mAbs being close to the NA and receptor-binding sites. MAbs to two other overlapping sites, 14 and 1 (which in turn, overlap site 12), inhibit HA quite effectively, and attachment to a lesser extent. Sites 14 and 1 probably identify a second domain involved in receptor recognition. MAbs to the two remaining sites (3 and 4), though neutralizing, are negative in all three assays, thus recognizing domains not involved in HA or NA or attachment to chick cells.