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

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

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

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.

Original languageEnglish
Pages (from-to)476-484
Number of pages9
JournalMicrobes and Infection
Volume19
Issue number9-10
DOIs
StatePublished - 1 Sep 2017

Keywords

  • 3R
  • Live viral vaccine
  • Neurite outgrowth
  • PDZ
  • Post-licensing safety test
  • Rabies virus

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