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Étude fonctionnelle des intéractions génétiques du virus Zika avec les réponses antivirales de l'hôte

Vincent Grass 1
1 Trafic Vésiculaire, Réponse Innée et Virus – Vesicular trafficking, Innate response
CIRI - Centre International de Recherche en Infectiologie - UMR
Abstract : Zika virus (ZIKV) infection causes neurological diseases and birth defects representing an important threat for human health. Recent studies demonstrated that interferon (IFN) response is pivotal for the control of ZIKV spread, its in utero transmission and protects against ZIKV-induced neurological diseases. It is necessary to understand the biology of this virus and what are the cellular responses involved. In infected cells, viruses are detected by receptors of the innate immune response, such as Toll-like receptors (TLRs). This recognition leads to the production of antiviral molecules, such as type I and III interferon (IFN). Recent work shows that activation of the TLR3 pathway contributes to controlling the spread of ZIKV and its pathogenesis. We have implemented an approach to map the interactions between the viral genome and different regulators and effectors of this antiviral response, including the TLR3 virus recognition steps. This approach is based on a combination of molecular biology and experimental evolution based on the high mutation rate of ZIKV and its rapid adaptation. I was able to highlight the appearance of a phenotype of ZIKV against the antiviral defenses of human cell lines that triggered resistance to activation of the TLR3 pathway and a better spread of the virus after 5 iterative passages. I was able to observe that the adapted viral population exhibited a loss of activation of antiviral responses (i.e. ISG15, MxA) 3h after infection. The implementation and validation of the CirSeq approach allows an analysis of the accuracy of high throughput sequencing data, as well as predicting the evolution of viral escape mechanisms.
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Submitted on : Friday, November 2, 2018 - 1:06:53 AM
Last modification on : Wednesday, November 20, 2019 - 3:26:21 AM
Long-term archiving on: : Sunday, February 3, 2019 - 12:42:03 PM


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  • HAL Id : tel-01910815, version 1


Vincent Grass. Étude fonctionnelle des intéractions génétiques du virus Zika avec les réponses antivirales de l'hôte. Virologie. Université de Lyon, 2018. Français. ⟨NNT : 2018LYSEN010⟩. ⟨tel-01910815⟩



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