Grant: Operating Grant

In response to viral infection, infected cells defend themselves by activating several families of cellular proteins known as transcription factors. These proteins have a role of messenger within the infected cells and will dictate if a particular gene will be used (induced) or not. Of these transcription factors, proteins named or called IRF3 and IRF7 play a key role as once turned-on or activated, they are responsible for the induction of genes with antiviral activities (known to impede pathogens' survival in the host). The latter are potent antiviral agents and powerful immunological modulators and understanding the cellular mechanisms by which infected cells produce these antiviral agents is required to identify novel cellular targets for future antiviral therapies. Discoveries in this particular field of research have demonstrated the essential roles of enzymes controlling the activity of IRF3 and IRF7. Notably, proteins called TBK1 and TRAF3 were shown to be of paramount importance in the establishment of an anti-viral defense system. Studies have demonstrated that cells infected with viruses are equipped with sensors that detect in incoming pathogens and relay this information to TRAF3, which is required for the activation of TBK1. Once activated, TBK1 is in turn responsible for the activation of IRF3 and IRF7. This type of regulation is referred as an activating signaling cascade, which control the induction of genes with antiviral activities. Albeit these important discoveries, how TRAF3, TBK1 and other "yet to discover key players" orchestrate and fine-tuned the antiviral cellular response is still largely unknown. Our endeavor in understanding the roles of TRAF3 and TBK1 in antiviral immunity as allowed us to discover other proteins with antiviral activity, namely TFG and mTOR. The propose research program will thus verify the implication of these proteins, which we believe to be essential effectors essential to fine-tune the antiviral cellular response.