Primary Supervisor: Prof. J. Hiscott, Istituto Pasteur-Rome, Italy
Title: The effect of dengue and SARS-CoV-2 infection on Nrf2 activation of the oxidative stress response
Collaborators: Prof. A. Bowie, Trinity College Dublin, Ireland; Dr. N. Manel, STIMUNITY, Paris, France
Early Stage Researcher: Magdalini Alexandridi


The activation of the antiviral and inflammatory signaling pathways has been linked to the production of reactive oxygen species (ROS) and metabolic stress induces cell death through (ROS)-induced apoptosis. Growing evidence demonstrates a model for redox homeostasis in which the ROS–antioxidant interaction acts as a metabolic interface for signals derived from metabolism and from the environment .  ROS have been implicated as both positive and negative modulators of the RLR signalling pathway of the innate immune system, with critical roles in NF-kB activation, activation of the NLRP3 inflammasome and modulation of antiviral innate immunity.  Because of the high reactivity of ROS, cells possess scavenger antioxidant mechanisms that maintain redox homeostasis. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a global transcriptional regulator involved in the maintenance of redox homeostasis through the control of basal and induced expression of an array of antioxidant enzymes. While ROS production promotes antiviral and inflammatory responses, we have demonstrated that activation of Nrf2, as well as the downstream antioxidant network, suppresses antiviral and inflammatory responses. It is our hypothesis that these redox regulatory checkpoints are activated by dengue virus infection (or SARS-CoV2) to inhibit the innate antiviral response and to facilitate virus replication. The aim of this project is to investigate the influence of dengue or SARS-CoV2 infections, and specific viral proteins, on the role of oxidative stress responses in regulation of immune- and metabolic responses,