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Study of C-C chemokine receptor 5 (CCR5) modulation by anti-HIV chemokine analogues

ContributorsBrodier, Hellena
Defense date2018
Abstract

CCR5 is a GPCR involved in the immune system, mostly known for being one of the main co-receptor for HIV type I entry into the cells. In the research for a potential anti-HIV drug, studies have developed super-agonists derived from the natural CCR5 ligand RANTES/CCL5 by modifying its N-terminal region, among them PSC-RANTES, 5P12-RANTES and 5P14-RANTES. This study consists of two projects focusing on the differences in CCR5 desensitization following treatment with this chemokine analogues. The aim of the first project was to confirm the differences obtained between RANTES/CCL5 and PSC-RANTES in their CCR5 occupancy after activation. The aim of the second project was to find if different phosphorylation patterns existed for CCR5. Serine to Alanine mutants were generated and tested using a BRET assay. No significant differences in the signalling patterns were found between the chemokines, hence rejecting the barcode hypothesis for CCR5, making receptor conformation changes a possible explanation for different post-endocytic pathways.

eng
Citation (ISO format)
BRODIER, Hellena. Study of C-C chemokine receptor 5 (CCR5) modulation by anti-HIV chemokine analogues. 2018.
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Master thesis
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  • PID : unige:112962
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