Caractérisation de l'expression des isoformes du DCIR dans l'infection par le VIH-1
|Abstract:||The C type lectin DCIR was identified as viral transfer factor from dendritic cells to CD4 T cells during HIV-1 infection. There are five known isoforms of the DCIR protein. The expression of some of these isoforms can be modulated independently in some pathologies. The hypothesis of this project is that DCIR isoforms can be modulated during HIV-1 infection and that it is possible to generate DCIR deficient cells with CRISPR/Cas9 technology. Our objectives were: to develop a specific quantitative PCR for each isoforms of DCIR; to quantify the expression of DCIR isoforms in immune cells of HIV-1 infected patients; to determine if there are correlations between the expression pattern of each isoform and the patients’ clinical data and; to develop a CRISPR/Cas9 tool allowing the knock out of the DCIR gene in hematopoietic stem cells. The results show that the expression of DCIR isoforms 1 to 4 is not modulated by HIV-1 infection. However, a positive correlation exists between the CD4/CD8 T cell ratio of treated HIV-1 patients and the expression of DCIR isoform 1 in polymorphonuclear cells. Furthermore, the DCIR isoforms 1 and 3 are the most expressed isoforms in the patients’ peripheral blood mononuclear cells, while the DCIR isoform 1 is the most expressed isoform in the patients’ polymorphonuclear cells. Finally, our CRISPR/Cas9 tool, allowing the inactivation of the DCIR gene in hematopoietic stem cells by lentiviral infection, has been developed. These results will allow us to better characterize the roles of DCIR isoforms, contributing so to the development of therapeutic strategies targeting this lectin.|
|Document Type:||Mémoire de maîtrise|
|Open Access Date:||13 December 2019|
|Collection:||Thèses et mémoires|
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