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Rabies virus binding to an acetylcholine receptor alpha-subunit peptide
1Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06510.
Journal of Molecular Recognition : JMR
|April 1, 1990
Summary
Rabies virus binds to nicotinic acetylcholine receptors, specifically targeting residues 173-204 on the alpha 1-subunit. This interaction, crucial for viral attachment, suggests potential antiviral strategies targeting this binding site.
Area of Science:
- Neuroscience
- Virology
- Biochemistry
Background:
- Rabies virus infects the central nervous system, utilizing host cell receptors for entry.
- Nicotinic acetylcholine receptors (nAChRs) are crucial for neurotransmission and are implicated as viral entry points.
Purpose of the Study:
- To investigate the molecular basis of rabies virus binding to the nicotinic acetylcholine receptor.
- To identify specific binding sites and explore potential antiviral targets.
Main Methods:
- Radioligand binding assays using 125I-labeled rabies virus and synthetic peptides of the nAChR alpha 1-subunit.
- Competition assays with unlabeled virus, snake venom neurotoxins, and synthetic peptides.
Main Results:
- Rabies virus binding to the nAChR alpha 1-subunit peptide (residues 173-204) was pH-dependent, saturable, and competed by homologous virus.
- Neurotoxins and nAChR peptides competed with virus binding, indicating shared binding sites.
- Highest affinity binding determinants for rabies virus were localized to residues 179-192.
- Binding to neuronal nAChRs was suggested by inhibition with a rat nerve alpha 3-subunit peptide.
Conclusions:
- Rabies virus and neurotoxins share binding sites on the nAChR alpha 1-subunit, specifically within residues 173-204.
- The identified binding region (residues 179-192) is a key determinant for rabies virus attachment.
- Synthetic peptides targeting this interaction could serve as novel antiviral agents to block rabies virus entry.