Antipeptide monoclonal antibodies inhibit the binding of rabies virus glycoprotein and alpha-bungarotoxin to the nicotinic acetylcholine receptor.
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.
Bracci
L
L
Dipartimento di Biologia Evolutiva Via P. A. Mattioli, Università di Siena, Italy.
Antoni
G
G
Cusi
M G
MG
Lozzi
L
L
Niccolai
N
N
Petreni
S
S
Rustici
M
M
Santucci
A
A
Soldani
P
P
Valensin
P E
PE
D000911:Antibodies, Monoclonal / Q000276:immunology; D001667:Binding, Competitive; D002038:Bungarotoxins / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006023:Glycoproteins / Q000276:immunology / Q000378:metabolism*; D010446:Peptide Fragments / Q000276:immunology*; D011820:Rabies virus / Q000378:metabolism*; D011950:Receptors, Cholinergic / Q000378:metabolism*; D014764:Viral Proteins / Q000276:immunology / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D002038:Bungarotoxins; D006023:Glycoproteins; D010446:Peptide Fragments; D011950:Receptors, Cholinergic; D014764:Viral Proteins