Botulinum neurotoxin light chains expressed by defective herpes simplex virus type-1 vectors cleave snare proteins and inhibit cgrp release in rat sensory neurons
| Autor: | Joussain, Charles, Le Coz, Olivier, Pichugin, Andrey, Marconi, Peggy, Lim, Filip, Sicurella, Mariaconcetta, Salonia, Andrea, Montorsi, Francesco, Wandosell, Francisco, Foster, Keith, Giuliano, François, Epstein, Alberto L., Muñoz, Alejandro Aranda |
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| Přispěvatelé: | Wings for Life, Agence Nationale de la Recherche (France) |
| Rok vydání: | 2019 |
| Předmět: |
Sensory neurons
Botulinum Toxins SNARE proteins Sensory Receptor Cells Calcitonin Gene-Related Peptide Genetic Vectors Neurotoxins lcsh:Medicine Herpesvirus 1 Human Article NO Rats Sprague-Dawley HSV-1 amplicon vectors Ganglia Spinal Animals Light chains transgenic botulinum neurotoxins Cells Cultured lcsh:R Biología y Biomedicina / Biología DRG HSV-1 amplicon vectors Light chains Sensory neurons SNARE proteins Transgenic botulinum neurotoxins sensory neurons nervous system light chains DRG Transgenic botulinum neurotoxins Female |
| Zdroj: | Biblos-e Archivo. Repositorio Institucional de la UAM Consejo Superior de Investigaciones Científicas (CSIC) Toxins Volume 11 Issue 2 Toxins, Vol 11, Iss 2, p 123 (2019) Digital.CSIC. Repositorio Institucional del CSIC instname |
| Popis: | A set of herpes simplex virus type 1 (HSV-1) amplicon vectors expressing the light chains (LC) of botulinum neurotoxins (BoNT) A, B, C, D, E and F was constructed. Their properties have been assessed in primary cultures of rat embryonic dorsal root ganglia (DRG) neurons, and in organotypic cultures of explanted DRG from adult rats. Following infection of primary cultures of rat embryonic DRG neurons, the different BoNT LC induced efficient cleavage of their corresponding target Soluble N-ethylmaleimide-sensitive-factor Attachment protein Receptor (SNARE) protein (VAMP, SNAP25, syntaxin). A similar effect was observed following infection by BoNT-A LC of organotypic cultures of adult rat DRG. To quantify and compare the functional activities of the different BoNT LC, the inhibition of calcitonin gene-related protein (CGRP) secretion was assessed in DRG neurons following infection by the different vectors. All BoNT-LC were able to inhibit CGRP secretion although to different levels. Vectors expressing BoNT-F LC displayed the highest inhibitory activity, while those expressing BoNT-D and -E LC induced a significantly lower CGRP release inhibition. Cleavage of SNARE proteins and inhibition of CGRP release could be detected in neuron cultures infected at less than one transducing unit (TU) per neuron, showing the extreme efficacy of these vectors. To our knowledge this is the first study investigating the impact of vector-expressed transgenic BoNT LC in sensory neurons. Wings for Life—Spinal Cord Research Foundation grant WFL-FR-07/17 –N◦154, by EU ERANET-Neuron grant N◦ ANR-16-NEU3-003, attributed to the ELPIS program, by the French Agence National pour la Recherche (ANR) grant N◦ ANR-10-IBHU-0006 |
| Databáze: | OpenAIRE |
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