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Construction d’un clone infectieux d’une souche méditerranéenne du Virus West Nile, validation de ses propriétés biologiques et développement de nouveaux modèles d’évaluation de la virulence

Abstract : West Nile virus (WNV) is a neurotropic virus mainly transmitted through mosquito bites. Wild birds represent the main reservoir hosts. Strains circulating in Europe belong to four lineages and have caused numerous but limited epidemics over the last few years. In 1998, an important outbreak associated to huge bird fatalities caused by a highly neuroinvasive strain (IS-98-ST1) took place in Israel. We aimed at producing a new infectious clone, based on the lineage 1a IS-98-ST1 WNV strain, for the characterization of its neuroinvasion properties as well as the molecular determinants of European WNV virulence. The growth kinetics of recombinant and parental WNV were similar in Vero cells. Moreover, the phenotypes of recombinant and parental WNV were indistinguishable in terms of viremia, viral load in the brain and mortality in susceptible and resistant mice. Finally, the pathobiology of the infectious clone was examined in embryonated chicken eggs, proposed as a new model for the evaluation of WNV virulence. The potential of human neuroblastoma cells (SK-N-SH) to discriminate between highly and mildly virulent WNV strains was assayed. In conclusion: a new molecular tool that is useful for the study of molecular determinants of WNV virulence has been generated. We take advantage of the high genetic stability of our one-piece infectious WNV cDNA clone to produce mutant viruses through the insertion of point mutations or the exchange of genetic fragments between WNV strains into the backbone of the IS-98-ST1 infectious clone.
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https://tel.archives-ouvertes.fr/tel-00747842
Contributor : ABES STAR :  Contact
Submitted on : Friday, November 2, 2012 - 11:52:16 AM
Last modification on : Monday, November 28, 2022 - 11:36:30 AM
Long-term archiving on: : Sunday, February 3, 2013 - 3:36:36 AM

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VA_BAHUON_CELINE_14092012.pdf
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  • HAL Id : tel-00747842, version 1
  • PRODINRA : 316781

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Céline Bahuon. Construction d’un clone infectieux d’une souche méditerranéenne du Virus West Nile, validation de ses propriétés biologiques et développement de nouveaux modèles d’évaluation de la virulence. Sciences agricoles. Université Paris Sud - Paris XI, 2012. Français. ⟨NNT : 2012PA114828⟩. ⟨tel-00747842⟩

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