Impact des agents réactivateurs de la latence sur la physiologie des macrophages et leur susceptibilité à l'infection par le VIH-1

Authors: Turmel, Marc-Olivier
Advisor: Tremblay, Michel J.
Abstract: Latency establishment in memory CD4+ T-lymphocytes is a major obstacle to HIV-1 eradication. Those infected, but poorly transcriptionally, cells are immune to combinatory antiretroviral therapy which target HIV-1 replication steps. Those therapie, therefore, don’t allow infected cells elimination. The Shock and Kill strategy, which relies on the use of agents that promote viral reactivation in latently infected cells is promising and could, theoretically, allow the elimination of HIV-1. However, the agents currently studied are non-discriminating towards the different cell populations, infected or not. In addition, the study of the impact of those agents on macrophages, which is a key cell population in the establishment of infection and progression of the disease, seems to have been neglected at the expense of studies specifically focused on CD4+ T lymphocytes. Our results have shown that the treatment of human primary macrophages with latency reactivating agents (LRAs), particularly the PKC activator bryostatin-1, is associated with a significant increase in the expression and secretion of pro-inflammatory mediators such as CCL2/MCP-1, CCL5/RANTES, IL-8/CXCL8 and TNF. These modulations are not observed in CD4+ T cells. In addition, the susceptibility of macrophages to HIV-1 infection is decreased following treatment with LRAs. Finally, the treatment of infected macrophages with bryostatin-1 is associated with a significant decrease in the production of viral particles. Those results show that the effect of LRAs on the different cell populations is very variable and that a better comprehension of the effects of these is necessary.
Document Type: Mémoire de maîtrise
Issue Date: 2018
Open Access Date: 28 November 2018
Grantor: Université Laval
Collection:Thèses et mémoires

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