ALTERNATIVE FORMS OF A STRAIN-SPECIFIC NEUTRALIZING ANTIGENIC SITE ON THE SINDBIS VIRUS-E2 GLYCOPROTEIN
ALTERNATIVE FORMS OF A STRAIN-SPECIFIC NEUTRALIZING ANTIGENIC SITE ON THE SINDBIS VIRUS-E2 GLYCOPROTEIN
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DOI：
10.1016/0042-6822(87)90175-9
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发表时间：
1987-11-01
期刊：
影响因子：
3.7
通讯作者：
JOHNSTON, RE
中科院分区：
文献类型：
--
作者：
DAVIS, NL;PENCE, DF;JOHNSTON, RE
用抗Sindbis病毒两种实验室毒株Sb和SIN的单抗进行的实验表明，在E2糖蛋白上存在一个毒株特有的中和抗原位点(E2-b)。通过对6个实验室菌株的单抗结合模式和E2糖蛋白基因序列的比较，区分出三种不同的E2-b构型，它们与E2糖蛋白第216位的特定氨基酸替换有关。用E2-b特异性抗体筛选的中和逃逸突变体的进一步研究证实，氨基酸216是E2-b抗原位点的主要决定因素。9个突变体中有8个在216位出现了编码变化。一个中和逃逸突变在第213位产生了一个新的糖基化位点，并导致了一个E2蛋白在SDS-PAGE中的迁移速度改变。所研究的中和逃逸突变包括在实验室菌株中没有发现的氨基酸替换，这些氨基酸替换显示了对两个E2-b特异性单抗的不同结合要求。E_2-b位点与先前描述的E_2-c中和抗原位点(R.A.Olmsted，W.J.Meyer和R.E.Johnston，1986，病毒学148,245-254)形成对比。
Experiments with monoclonal antibodies raised against two laboratory strains of Sindbis virus, SB and SIN, suggested the existence of a strain-specific neutralizing antigenic site (E2-b) on the E2 glycoprotein. A comparison of monclonal antibody binding patterns and E2 glycoprotein gene sequences of six laboratory strains distinguished three different configurations of E2-b that correlated with specific amino acid substitutions at position 216 of the E2 glycoprotein. Further study of neutralization escape mutants selected with E2-b-specific antibodies confirmed that amino acid 216 is a major determinant of the E2-b antigenic site. Eight of nine mutants showed a coding change at position 216. One neutralization escape mutation created a new glycosylation site at position 213 and resulted in an E2 protein with an altered migration rate in SDS-PAGE. The neutralization escape mutants studied included amino acid substitutions not found in the laboratory strains that revealed differing binding requirements for two E2-b-specific monoclonal antibodies. The E2-b site is contrasted with the E2-c neutralizing antigenic site described previously (R. A. Olmsted, W. J. Meyer, and R. E. Johnston, 1986, Virology 148, 245-254).