USE OF MONOCLONAL-ANTIBODIES TO IDENTIFY 4 NEUTRALIZATION IMMUNOGENS ON A COMMON COLD PICORNAVIRUS, HUMAN RHINOVIRUS-14
USE OF MONOCLONAL-ANTIBODIES TO IDENTIFY 4 NEUTRALIZATION IMMUNOGENS ON A COMMON COLD PICORNAVIRUS, HUMAN RHINOVIRUS-14
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DOI：
10.1128/jvi.57.1.246-257.1986
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发表时间：
1986-01-01
影响因子：
5.4
通讯作者：
RUECKERT, RR
中科院分区：
文献类型：
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作者：
SHERRY, B;MOSSER, AG;RUECKERT, RR
用35株抗人鼻病毒14号(HRV-14)的小鼠单抗，筛选出62株中和抗性突变体。当在中和试验中与抗体交叉测试时，突变体分为四个抗原组，这里称为中和免疫原：NIM-IA、-IB、-II和-III。对与血清型可变区对应的片段中的突变RNA进行测序发现，氨基酸替换分离成簇，这与免疫原基(VP1氨基酸残基91或95处的Nim-IA突变；VP2残基158、159、161或162处的Nim-II突变；VP3残基72、75或78处的Nim-III突变；以及VP1残基83或85处的Nim-IB突变，或残基138或139处的Nim-IB突变)完全相关。对病毒的三维结构(M.G.Rossmann，E.Arnold，J.W.Erickson，E.A.Frankenberger，J.P.Griffith，H.-J.Hecht，J.E.Johnson，G.Kamer，M.Luo，A.G.Mosser，R.R.Rueckert，B.Sherry和G.Vriend，Nature[London]，317：145-153,1985)的研究表明，每个取代簇从病毒表面形成一个突起，取代氨基酸的侧链指向外部。此外，四个氨基酸替换最初看起来是异常的，因为它们被编码在簇群之外，可以追溯到紧邻适当病毒突起的表面位置。我们得出结论，四种抗原中有三种是不连续的，即Nim-IB、-II和-III。因此，所有62个突变体中的氨基酸替换都落在建议的免疫原点内；没有证据表明远端突变改变了任何抗原点。
A collection of 35 mouse monoclonal antibodies, raised against human rhinovirus 14 (HRV-14), was used to isolate 62 neutralization-resistant mutants. When cross-tested against the antibodies in a neutralization assay, the mutants fell into four antigenic groups, here called neutralization immunogens: NIm-IA, -IB, -II, and -III. Sequencing the mutant RNA in segments corresponding to serotype-variable regions revealed that the amino acid substitutions segregated into clusters, which correlated exactly with the immunogenic groups (NIm-IA mutants at VP1 amino acid residue 91 or 95; NIm-II mutants at VP2 residue 158, 159, 161, or 162; NIm-III mutants at VP3 residue 72, 75, or 78; and NIm-IB mutants at two sites, either VP1 residue 83 or 85, or residue 138 or 139). Examination of the three-dimensional structure of the virus (M. G. Rossmann, E. Arnold, J. W. Erickson, E. A. Frankenberger, J. P. Griffith, H.-J. Hecht, J. E. Johnson, G. Kamer, M. Luo, A. G. Mosser, R. R. Rueckert, B. Sherry, and G. Vriend, Nature [London], 317:145-153, 1985) revealed that each of the substitution clusters formed a protrusion from the virus surface, and the side chains of the substituted amino acids pointed outward. Moreover, four of the amino acid substitutions, which initially appeared to be anomalous because they were encoded well outside the cluster groups, could be traced to surface positions immediately adjacent to the appropriate viral protrusions. We conclude that three of the four antigens, NIm-IB, -II, and -III, are discontinuous. Thus, the amino acid substitutions in all 62 mutants fell within the proposed immunogenic sites; there was no evidence for alteration of any antigenic site by a distal mutation.