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Caractérisation des étapes précoces de l'entrée du VIH-1 dans les cellules dendritiques

Abstract : The Human Immunodeficiency Virus type I (HIV-I) is mostly degraded in dendritic cells as soon as it enters. Previous work in the team shows that the mechanism of autophagy contributes to viral degradation (virophagy) and promotes innate and adaptive immune responses. Since this virophagy is subsequently inhibited by the virus in dendritic cells, a better understanding of the implementation of this antiviral autophagy is essential in order to promote and above all stabilize cellular defenses. Our results show that DC-SIGN, a C-type lectin receptor (CLR) that recognizes mannosylated or fucosylated carbohydrates, may be involved in the development of this antiviral autophagy. Thus, we show that after recognition of HIV, this receptor induces autophagy and interacts rapidly with several autophagic proteins, some of which are involved in the endosomal pathways. Indeed, we show for the first time the association of the protein Atg9 with the internalized DC-SIGN receptor. The Atg9 protein is an essential factor in the initiation of the autophagic pathway regulating in particular the supply of membranes originating from the plasma membrane for the nucleation of vesicles linked to the autophagic pathway. On the other hand, after a mass spectrometric study of the internalized DC-SIGN receptor interbody, we show that an E3 ligase belonging to the TRIM family, TRIM25, is recruited during endocytosis of the receptor. This protein has been reported to be involved in the regulation of antiviral innate responses from the RIG-I pathogen recognition receptor suggesting an essential function of TRIM25 in innate immune responses. Interestingly, some members of the TRIM family have recently been shown to be essential for the induction of a form of selective autophagy, sometimes antiviral, precision autophagy. In this sense, we show that a complex is formed between the DC-SIGN, Atg9 and TRIM25 receptors, suggesting that autophagy early on engagement of the DC-SIGN receptor could be selective. All these elements constitute a first step for a better understanding of the early stages of the entry of HIV into dendritic cells with the characterization of a selective virophagy induced when a receptor of the innate immunity And which represents a particularly interesting target in order to improve certain therapeutic strategies currently being developed.
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Submitted on : Monday, January 15, 2018 - 12:24:34 PM
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  • HAL Id : tel-01684252, version 1

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Laure Papin. Caractérisation des étapes précoces de l'entrée du VIH-1 dans les cellules dendritiques. Sciences agricoles. Université Montpellier, 2017. Français. ⟨NNT : 2017MONTT030⟩. ⟨tel-01684252⟩

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