Iorio R M, Glickman R L, Riel A M, Sheehan J P, Bratt M A
Department of Molecular Genetics and Microbiology, University of Massachusetts Medical School, Worcester 01605.
Virus Res. 1989 Jul;13(3):245-61. doi: 10.1016/0168-1702(89)90019-1.
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 to 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.
我们之前已在新城疫病毒澳大利亚 - 维多利亚分离株的血凝素 - 神经氨酸酶(HN)糖蛋白上鉴定出五个抗原位点(Iorio和Bratt,《病毒学杂志》48卷,440 - 450页;Iorio等人,《普通病毒学杂志》67卷,1393 - 1403页)。现在又描述了另外两个位点(命名为12和23),使得我们的中和抗HN抗体组所定义的抗原位点总数达到七个。竞争抗体结合和累加中和试验表明,这些新鉴定出的每个位点都与两个先前定义的位点重叠。因此,这七个HN抗原位点在分子的三维构象中形成一个连续体。对血凝素(HA)抑制、神经氨酸酶(NA)以及病毒与鸡细胞单层附着的抑制研究已被用于构建每个抗原位点功能概况。针对三个重叠位点(12、2和23)的单克隆抗体(mAb)抑制HA和NA,并阻止病毒附着到鸡细胞单层。这些发现与这些mAb所识别的结构域靠近NA和受体结合位点一致。针对另外两个重叠位点14和1(它们又与位点12重叠)的mAb相当有效地抑制HA,对附着的抑制作用较小。位点14和1可能确定了参与受体识别的第二个结构域。针对其余两个位点(3和4)的mAb虽然具有中和作用,但在所有这三种试验中均呈阴性,因此识别的是不参与HA、NA或与鸡细胞附着的结构域。