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

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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Submitted on : Wednesday, May 2, 2018 - 3:43:14 PM
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Wonhyo Seo, Christophe Prehaud, Zakir Khan, Claude Sabeta, Monique Lafon. Investigation of rabies virus glycoprotein carboxyl terminus as an in vitro predictive tool of neurovirulence. A 3R approach.. Microbes and Infection, Elsevier, 2017, 19 (9-10), pp.476 - 484. ⟨10.1016/j.micinf.2017.05.006⟩. ⟨pasteur-01783671⟩

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