PhD defense of Grégorie Lebeau on December 14th 2023

Grégorie LEBEAU defended his PhD thesis on Thursday, December 14, 2023, at 2 p.m. in room C018 at the University of Reunion Island (Terre-Sainte campus).

Influence of cellular metabolism on the antiviral response targeting ZIKV and DENV Flaviviruses

Abstract: The objective of my thesis work was to characterize the interactions between two significant flaviviruses, Dengue virus (DENV) and Zika virus (ZIKV), and their human host. The former represents the greatest global threat with over 390 million cases per year and 2 billion people potentially at risk. While the latter has shown alarming growth in recent years, transitioning from a few sporadic cases recorded in the last century to larger-scale epidemics in the Pacific and South America between 2007 and 2015. Although the majority of infections by these viruses are asymptomatic or mildly symptomatic, mainly presenting with a flu-like syndrome (skin rashes, fever, joint pain), what is concerning is the small but significant proportion of severe cases that can occur, potentially overwhelming healthcare systems, as was the case during the COVID-19 pandemic. The antiviral response developed by the infected cell is a means of controlling the infection and limiting its deleterious effects. In recent years, the concept of immunometabolism has highlighted the critical role that cellular metabolism plays in immune cell activation as well as in the development of immune programs. This work provided an opportunity for us to investigate the importance of oxidative metabolism in both the interferon response and the antioxidant response, using an in vitro model, and to discuss the pathophysiological consequences of the virus's control over these responses. I was able to demonstrate that glutaminergic metabolism and oxidative phosphorylation play a crucial role in establishing a bivalent regulation of the interferon response, particularly in the context of ZIKV and DENV infection. However, dysregulated oxidative metabolism could be a source of deleterious effects during infection, as we showed for ZIKV, through the formation of intracellular aggregates, concurrent with a decrease in cellular antioxidant capacities.

Members of the jury
Pr. Laurent Chatel-Chaix (Reviewer)
Pr. Marie-Edith Lafon (Reviewer)
Pr. Christian Lefebvre D'Hellencourt (Examiner)
Dr. Marie Flamand (Examiner)
Dr. Marjolaine Roche (Thesis co-supervisor)
Dr. Wildriss Viranaicken (Thesis supervisor)