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Theses

Origine de la pathogénicité des lagovirus : avancées sur la diversité génétique virale et le développement d’un système de génétique inverse

Abstract : Lagoviruses infect leporidae (rabbits and hares). Pathogenic lagoviruses such as Rabbit haemorrhagic disease virus (RHDV) and European Brown Hare Syndrome virus (EBHSV) often cause fatal viral hepatitis with serious economic and ecological consequences. Non-pathogenic lagoviruses such as European Rabbit Caliciviruses 1 and 2 (RCV-E1 and RCV-E2) and Hare Caliciviruses (HaCV) cause no disease in rabbits and hares, respectively. The emergence of a new pathogenic lagovirus in 2010, named RHDV2, infecting both rabbits and hares, led us to question the origin of lagoviruses pathogenicity. The studied hypothesis is the evolution from non-pathogenic to pathogenic strains. For this purpose, the genetic diversity of non-pathogenic lagoviruses, little known in hares, was studied in this species. Eleven new gene sequences encoding the capsid protein and the first complete genome sequence of a HaCV virus have been obtained. These data showed the high genetic diversity of HaCVs and revealed their circulation long before the first detection of EBHSV in 1980. However, no evolutionary link was found between HaCV and EBHSV. New sequences of complete genomes or coding regions of RCV-E1 and RHDV2 were also characterized. Genetic analyses suggested that a recombination event between an RCV-E1 virus and an unknown virus was at the origin of the emergence of RHDV2. In the second part of the thesis, we attempted to develop a new reverse genetics (RG) system for the RHDV in order to study the molecular basis of the pathogenicity of lagoviruses. The in vivo genotype and phenotype of a reference RHDV strain were characterized and then in vitro and in vivo regeneration assays of this strain in RG were performed to validate the system under development. The results showed that the system was able to produce viral RNA and capsid protein in vitro. In vivo assay to regenerate the virus did not result in the infection of rabbits. However, the majority of the animals seroconverted. These results did not lead to the conclusion that the RG system was able to produce infectious viral particles and points for improvement are proposed.
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Submitted on : Wednesday, March 3, 2021 - 3:26:09 PM
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Clément Droillard. Origine de la pathogénicité des lagovirus : avancées sur la diversité génétique virale et le développement d’un système de génétique inverse. Microbiologie et Parasitologie. Université Rennes 1, 2020. Français. ⟨NNT : 2020REN1B016⟩. ⟨tel-03157952⟩

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