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Mécanismes déployés par le virus Zika dans le contrôle de l’apoptose lors de l’infection

Abstract : The goal of this thesis was to characterize the interactions between Zika virus (ZIKV) and its human host by studying several cellular responses, apoptosis, and Unfold protein responses UPR during in vitro infection of epithelial cells and to discuss the pathophysiological consequences in the modulation of viral infection. ZIKV is an arbovirus belonging to the genus flavivirus, transmitted primarily by Aedes mosquitoes and responsible for Zika virus disease. ZIKV was discovered in the 1950’s and was thought to cause sporadic disease in Africa, where infections were considered mild, manifesting only as mild flu-like symptoms (rash, fever, arthralgia). ZIKV suddenly gained international attention due to its emergence in Asia in 2007 followed by a very dramatic epidemic spread that affected several million people worldwide in less than 10 years, the vast majority in 2015-2016 in Brazil. It was also identified as a public health emergency by WHO in 2015 due to the increase in severe neurological sequelae such as Guillain-Barré syndrome in adults and previously unknown congenital syndromes (SCZ) such as microcephaly in newborns of mothers infected during pregnancy. The molecular mechanisms associated with epidemic emergence and pathogenicity of ZIKV had been only minimally studied before the 2015 Brazilian epidemic. The cytopathic effect induced by the virus in host cells plays a major role in pathogenesis, but is also beneficial, promoting the body’s elimination of the virus and the eventual resolution of infection. By characterizing programmed cell death during in vitro infection kinetics, I was able to show that apoptosis is delayed by ZIKV infection, allowing the virus to maintain a favorable anti-apoptotic state through the stabilization of the Bcl-2 protein. I also demonstrated that ZIKV was able to modulate the UPR in response to ER stress and interfere with the pro-apoptotic program driven by CHOP factor. These data demonstrate the important rôle of cellular hijacking during certain viral infections, and shed light on some of the mechanisms that could lead to the persistance of ZIKV infections and ZIKV disease symptoms. My findings additionally identify cellular pathways specific to ER stress and apoptosis as potential drug targets for the treatment of ZIKV infections.
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https://tel.archives-ouvertes.fr/tel-03403907
Contributor : Abes Star :  Contact
Submitted on : Tuesday, October 26, 2021 - 1:42:11 PM
Last modification on : Thursday, October 28, 2021 - 2:28:28 PM

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2021LARE0017_J_TURPIN.pdf
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  • HAL Id : tel-03403907, version 1

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Jonathan Turpin. Mécanismes déployés par le virus Zika dans le contrôle de l’apoptose lors de l’infection. Virologie. Université de la Réunion, 2021. Français. ⟨NNT : 2021LARE0017⟩. ⟨tel-03403907⟩

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