MUTATIONS CONFERRING RESISTANCE TO NEUTRALIZATION WITH MONOCLONAL-ANTIBODIES IN TYPE-1 POLIOVIRUS CAN BE LOCATED OUTSIDE OR INSIDE THE ANTIBODY-BINDING SITE
MUTATIONS CONFERRING RESISTANCE TO NEUTRALIZATION WITH MONOCLONAL-ANTIBODIES IN TYPE-1 POLIOVIRUS CAN BE LOCATED OUTSIDE OR INSIDE THE ANTIBODY-BINDING SITE
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DOI：
10.1128/jvi.57.1.81-90.1986
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发表时间：
1986-01-01
影响因子：
5.4
通讯作者：
HORAUD, F
中科院分区：
文献类型：
--
作者：
BLONDEL, B;CRAINIC, R;HORAUD, F
从野生型(马奥尼)和减毒(萨宾)1型传染性脊髓灰质炎病毒中筛选出对8种中和单抗具有抗原性的变异体。交叉免疫沉淀揭示了交叉中和未检测到的表位之间的相互关系。对抗原变异体的操作分析表明，所研究的8个中和表位中有7个是相互关联的。只有一个名为KC的中和表位与所有其他表位独立变化。后者被C3中和单抗识别，不仅存在于感染性病毒粒子上，而且存在于热变性(C抗原)颗粒和分离的衣壳蛋白VP1上。表位中和功能的丧失并不一定是由于其抗体结合能力的丧失。这种潜在的但不具有功能的中和表位自然存在于马奥尼和萨宾1号病毒上。在非中和单抗和抗鼠免疫球蛋白抗体存在的情况下，通过分离抗原变体可以破坏它们的抗体结合性。通过对其基因组的序列分析，定位了导致获得中和抗性的抗原变异体中的单点突变。在C3中和单抗存在下选择的突变体总是位于VP1第100位氨基酸的抗体结合位点(VP1的第93到103位)内。相反，在只与D抗原颗粒反应的中和性单抗存在的情况下，选择的抗原变异体在抗体结合位点(VP1的第93至103残基)之外的VP3处发生突变。马奥尼到Sabin 1表位图的完全转换是由于VP3第60位的苏氨酸到赖氨酸的替换。
Antigenic variants resistant to eight neutralizing monoclonal antibodies were selected from wild (Mahoney) and attenuated (Sabin) type 1 infectious poliovirions. Cross-immunoprecipitation revealed interrelationships between epitopes which were not detected by cross-neutralization. Operational analysis of antigenic variants showed that seven of eight neutralization epitopes studied were interrelated. Only one neutralization epitope, named Kc, varied independently from all the others. This latter, recognized by C3 neutralizing monoclonal antibody, was present not only on infectious virions but also on heat-denatured (C-antigenic) particles and on isolated capsid protein VP1. Loss of the neutralization function of an epitope did not necessary result from the loss of its antibody-binding capacity. Such potential, but not functional, neutralization epitopes exist naturally on Mahoney and Sabin 1 viruses. Their antibody-binding property could be disrupted by isolating antigenic variants in the presence of the nonneutralizing monoclonal antibody and anti-mouse immunoglobulin antibodies. Single-point mutations responsible for the acquisition of resistance to neutralization in the antigenic variants were located by sequence analyses of their genomes. Mutants selected in the presence of C3 neutralizing monoclonal antibody always had the mutation located inside the antibody-binding site (residues 93 through 103 of VP1) at the amino acid position 100 of VP1. On the contrary, antigenic variants selected in the presence of neutralizing monoclonal antibodies reacting only with D-antigenic particles had mutations situated in VP3, outside the antibody-binding site (residues 93 through 103 of VP1). The complete conversion of the Mahoney to the Sabin 1 epitope map resulted from a threonine-to-lysine substitution at position 60 of VP3.