Bracci L, Antoni G, Cusi M G, Lozzi L, Niccolai N, Petreni S, Rustici M, Santucci A, Soldani P, Valensin P E
Dipartimento di Biologia Evolutiva Via P. A. Mattioli, Università di Siena, Italy.
Mol Immunol. 1988 Sep;25(9):881-8. doi: 10.1016/0161-5890(88)90125-3.
It has been reported that binding to muscle nicotinic acetylcholine receptor at the post-synaptic membrane is an important event of the rabies virus neurotropism. The binding site can be located within the 190-203 region of the virus glycoprotein sharing a high degree of homology with the "toxic loop" of the curare-mimetic snake neurotoxins. We have synthesized a tetradecapeptide corresponding to this glycoprotein region and used it, following conjugation with an immunogenic carrier to raise MAbs. We found that some MAbs raised against the peptide were able to recognize both the virus glycoprotein and the snake neurotoxin alpha-bungarotoxin; moreover, they can inhibit the binding of rabies virus glycoprotein and alpha-bungarotoxin to the nicotinic acetylcholine receptor extracted from the electric organs of Torpedo marmorata. On the basis of this cross-reactivity, we suggest that rabies virus glycoprotein and curare-mimetic snake neurotoxins share three-dimensionally similar structures in order to bind to the nicotinic cholinergic receptor. The potential use of the immunogenic properties of the peptide for the rational design of a synthetic vaccine against rabies is proposed.
据报道，狂犬病毒嗜神经性的一个重要事件是其与突触后膜上的肌肉烟碱型乙酰胆碱受体结合。该结合位点可能位于病毒糖蛋白的190 - 203区域内，此区域与箭毒样蛇神经毒素的“毒性环”具有高度同源性。我们合成了对应于该糖蛋白区域的十四肽，并在将其与免疫原性载体偶联后用于制备单克隆抗体。我们发现，一些针对该肽产生的单克隆抗体能够识别病毒糖蛋白和蛇神经毒素α - 银环蛇毒素；此外，它们能够抑制狂犬病毒糖蛋白和α - 银环蛇毒素与从电鳐电器官中提取的烟碱型乙酰胆碱受体的结合。基于这种交叉反应性，我们认为狂犬病毒糖蛋白和箭毒样蛇神经毒素在三维结构上具有相似性，以便与烟碱型胆碱能受体结合。本文提出了利用该肽的免疫原性特性合理设计狂犬病合成疫苗的可能性。
