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鉴定和表位作图分析抗口蹄疫病毒 A24 Cruzeiro 株的中和性单克隆抗体。

Characterisation and epitope mapping of neutralising monoclonal antibodies to A24 Cruzeiro strain of FMDV.

机构信息

Institute for Animal Health, Pirbright Laboratory, Ash Road, Woking, Surrey GU24 0NF, UK.

出版信息

Vet Microbiol. 2011 Apr 21;149(1-2):242-7. doi: 10.1016/j.vetmic.2010.11.003. Epub 2010 Nov 9.

DOI:10.1016/j.vetmic.2010.11.003
PMID:21144677
Abstract

Characterisation of seven neutralising monoclonal antibodies (mAbs) produced against foot-and-mouth disease virus A(24) Cruzeiro revealed three reactivity groups. Gr-I recognised linear epitopes where as Gr-II was conformation-dependent and trypsin-insensitive. The Gr-III was also conformation-dependent, but trypsin-sensitive. Mar (mAb neutralisation resistant)-mutants could only be produced against Gr-I and Gr-III mAbs. Capsid sequence comparison of Gr-I mar-mutants with parent virus revealed changes in the G-H loop of VP1 at positions 141, 143 and 147. Similarly, a Gr-III mar-mutant showed a change from a highly conserved glycine to a tryptophan at position 148 of VP1 along with three additional changes at the N-terminus of VP1, VP2 and VP4. This residue at 148 of VP1 is located at +2 position after "RGD" and is equivalent to the position identified by the mAb recognising site 5 in serotype O viruses. This site is probably formed because of the interaction of the G-H loop with other residues in different structural proteins.

摘要

针对口蹄疫病毒 A(24) Cruzeiro 产生的七种中和单克隆抗体(mAb)的特性研究表明,存在三个反应性组。Gr-I 识别线性表位,Gr-II 是构象依赖性的,且对胰蛋白酶不敏感。Gr-III 也是构象依赖性的,但对胰蛋白酶敏感。仅能针对 Gr-I 和 Gr-III mAb 产生 Mar(mAb 中和抗性)突变体。Gr-I mar-突变体与亲本病毒的衣壳序列比较显示,VP1 的 G-H 环在位置 141、143 和 147 处发生变化。同样,Gr-III mar-突变体在 VP1 的位置 148 处从高度保守的甘氨酸突变为色氨酸,同时在 VP1、VP2 和 VP4 的 N 端还有另外三个变化。VP1 上的这个位置 148 位于“RGD”之后的+2 位,与 O 型病毒中 mAb 识别位点 5 所识别的位置相同。由于 G-H 环与其他结构蛋白中的不同残基相互作用,可能形成了这个位点。

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