Pierre-Olivier VIDALAIN, CIRI, Lyon

Glycolytic enzymes and the pyrimidine biosynthesis pathway: two examples of functional interactions between metabolism and innate immunity

Pierre-Olivier VIDALAIN, PhD invited by Karim Si-Tayeb (Eq IV) Université Lyon 1, ENS Lyon

Abstract

Interferons are key players of the innate immune response against viruses and tumor cells. These cytokines control hundreds of Interferon-Stimulated Genes (ISGs) that encode cellular factors repressing directly or indirectly viral replication and tumorigenesis. To isolate small compounds inducing interferons and/or ISGs through yet unidentified pathways, we screened large chemical libraries of synthetic molecules from different sources. This allowed the identification of four chemical series exhibiting immunostimulatory properties. These molecules were later characterized as inhibitors of de novo pyrimidine biosynthesis, thus establishing some unexpected functional link between this metabolic pathway and the interferon response. More recently, the team showed that innate immunity in hepatocellular carcinoma cells is reprogrammed by an isoenzyme switch of hexokinases, the enzymes catalyzing the initial step of glycolysis. Altogether, our results illustrate the functional interactions between metabolic pathways and the interferon response, opening new perspectives for the development of antiviral and cancer therapies.

Biography

Pierre-Olivier Vidalain, Research Director, CNRS (Centre National de la Recherche Scientifique). After his Ph.D in immunology (Ecole Normale Supérieure de Lyon), Pierre-Olivier joined Pr. Marc Vidal's team (Harvard Medical School, Boston) where he was trained to high-throughput screening techniques and protein-protein interaction analysis. Recruited in 2005 at the CNRS, he worked successively at the Institut Pasteur and the Université Paris Descartes where he studied interactions between viral and cellular proteins and developed multiple assays for the identification of antiviral compounds targeting host factors. He has a special interest in the immunomodulatory properties of small compounds inhibiting the pyrimidine biosynthesis pathway. In January 2019, he joined the « Centre International de Recherche en Infectiologie » in Lyon to continue his work at the interface between innate antiviral immunity, metabolism and chemobiological approaches.