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Rôle de l'autophagie sélective au cours de l'infection par le VIH-1 des lymphocytes T CD4

Abstract : Autophagy is an ubiquitous degradation pathway involved in innate immunity. Numerouspathogens have therefore developed strategies to block or use the autophagy machinery to their own benefit. This degradation can be highly selective, thanks to the intervention of autophagy receptors, like p62/SQSTM1, involved in the specific targeting of substrates to autophagosomes after their interaction with the ATG8 family of autophagic proteins. Our team has demonstrated that the HIV‐1 envelope proteins (Env) are responsible for autophagy triggering in CD4 T lymphocytes. If the target cells become productively infected, the autophagy process is blocked by the virus. During my thesis, we report that autophagy exerts an anti‐HIV effect by selectively degrading the HIV‐1 transactivator Tat, via its interaction withp62. On the contrary, if the target cells are not productively infected because the viral cycle is interrupted after the entry step, autophagy is not controlled and leads to apoptosis. These results suggest that the degradation of cellular components could be responsible for the induction of apoptosis. My thesis work indicates that Env induces an oxidative stress in the uninfected target cells and that this stress is involved in their death. Our preliminary results suggest that the peroxisomes would be targeted to autophagic degradation in these conditions. As these organelles are involved in the detoxification of the cells, we have made the assumption that Env‐induced autophagy triggers the selective degradation of these peroxisomes that leads to the accumulation of reactive oxygen species, and ultimately to apoptotic cell death.
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Submitted on : Thursday, July 6, 2017 - 12:52:26 PM
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  • HAL Id : tel-01557546, version 1



Coralie Daussy. Rôle de l'autophagie sélective au cours de l'infection par le VIH-1 des lymphocytes T CD4. Médecine humaine et pathologie. Université Montpellier, 2016. Français. ⟨NNT : 2016MONTT071⟩. ⟨tel-01557546⟩



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