Investigation of rabies virus glycoprotein carboxyl terminus as an in vitro predictive tool of neurovirulence. A 3R approach
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Date
Authors
Seo, Wonhyo
Prehaud, Christophe
Khan, Zakir
Sabeta, Claude Taurai
Lafon, Monique
Journal Title
Journal ISSN
Volume Title
Publisher
Elsevier
Abstract
In the field of live viral vaccines production, there is an unmet need for in vitro tests complying a 3R approach (Refine, Replace and Reduce the use of animal experimentation) to replace the post-licensing safety tests currently assayed in animals. Here, we performed a pilot study evaluating whether virulence of rabies virus, RABV, can be forecast by an in vitro test of neurite outgrowth. The rationale to use neurite outgrowth as a read-out for this test is based on the salient property of the cytoplasmic domain of the G-protein (Cyto-G) of virulent RABV strains – not of attenuated RABV strains – to stimulate neurite outgrowth in vitro. We observed that neurite elongation triggered by the Cyto-Gs encoded by different RABV field isolates correlate with the distinct virulence scores obtained in a mouse model of experimental rabies. Our results cast the idea that it could be feasible to predict RABV virulence by testing the in vitro property of a RABV strain to promote neurite outgrowth without the use of animal experimentation.
Description
Keywords
3R, Post-licensing safety test, Live viral vaccine, Neurite outgrowth, PDZ, Rabies virus (RABV)
Sustainable Development Goals
Citation
Seo, W., Prehaud, C., | Khan, Z., Sabeta, C.T. & Lafon. M. 2017, 'Investigation of rabies virus glycoprotein carboxyl terminus as an in vitro predictive tool of neurovirulence. A 3R approach', Microbes and Infection, vol. 19, no. 9-10, pp. 476-484.