Investigation of rabies virus glycoprotein carboxyl terminus as an in vitro predictive tool of neurovirulence. A 3R approach

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Authors

Seo, Wonhyo
Prehaud, Christophe
Khan, Zakir
Sabeta, Claude Taurai
Lafon, Monique

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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.

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Keywords

3R, Post-licensing safety test, Live viral vaccine, Neurite outgrowth, PDZ, Rabies virus (RABV)

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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.