Phd defence of Olivia Guillin on Friday 10th of December 2021 at 14pm.
Impact of zinc isotopes and selenium during HIV-1 infection
Selenium and zinc are two micronutrients essential for numerous physiological and cellular processes. Viruses disrupt the nutrient homeostasis in living organisms they infect, especially the Human Immunodeficiency Virus (HIV), the etiological agent of the Acquired ImmunoDeficiency Syndrome (AIDS). Several epidemiological studies have highlighted selenium and zinc deficiencies in patients, showing their importance during this viral infection. These nutrients act differently in Humans; selenium is present in only 25 proteins, named selenoproteins, and is incorporated in the form of an amino acid, the selenocysteine. Selenoproteins are implicated in the regulation of redox homeostasis in cells and reactive oxygen species detoxification, both pathways being very important during viral infection. Zinc is a cofactor for approximately 3000 human proteins and is important for the structure of zinc finger domains. Zinc finger proteins are implicated in various functions requiring nucleic acid interactions. Among them, NCp7, the HIV-1 nucleocapsid protein is a zinc finger protein essential for the viral structure. Therefore, it is believed that significant amount of zinc accumulates into viral particles. The isotopic fractionation is defined as the partitioning of heavy and light isotopes after a process. Recent studies have highlighted it in biological processes and have observed it in physiological or pathological context such as cancers but not yet during viral infections. This project is organized around these two essential nutrients during HIV-1 infection of T CD4+ lymphocytes. The first axis of my thesis emphasizes the role of selenium and selenoproteins in a cellular model. Our results show that the selenium levels, in addition to regulate selenoproteins expression, influence HIV-1 replication. On the other hand, infection modulates selenoproteins expression. The second axis which is at a crossroad between geochemistry and biology, investigates the zinc isotopic fractionation during HIV-1 infection. Our results show that viruses are enriched in zinc light isotopes in our cellular model. Furthermore, viruses enriched in light isotopes are more infectious than those enriched in heavy isotopes. Our work aims at characterizing zinc and selenium implication during HIV-1 infection of CD4+ T lymphocytes. This will provide us with a better understanding of the importance of selenium and zinc in HIV-patients, and particularly the way the virus interferes with the homeostasis of these nutrients.
Jury:
Caroline GOUJON Chargée de recherche - IRIM Rapporteure
Alexandra GOURLAN MCU - Univ. Grenoble-Alpes Rapporteure
Delphine MURIAUX Directrice de recherche - IRIM Examinatrice
Edmond DERRINGTON Professeur - UCBL Examinateur
Pierre JALINOT Directeur de recherche - LBMC Examinateur
Laurent CHAVATTE Directeur de recherche - CIRI Directeur de thèse