Etudes structurales des interactions virus-hôte à travers deux exemples : le récepteur du système immunitaire inné RIG-I et le domaine endonucléase de l'ARN polymérase du virus de la grippe

TL;DRAbstract

The first line of defense against invading pathogens in the human body is the innate im- mune system. Astonishingly, with only a handful of different pathogen recognition recep- tors (around 50), the innate immune system is able to detect a remarkably broad variety of pathogen specific molecules to trigger protective pathways and to activate the adaptive immune system. In the case of intruding viruses, two families of pattern recognition re- ceptors (PRRs) are active: retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs) and Toll-like receptors (TLRs). The family of RIG-I like receptors includes the proteins RIG-I, MDA5 and LGP2, which recognize viral RNA in the cytosol. In the first part of this thesis, aspects of the RIG-I pathway are discussed: With which RNA does RIG-I interact and how? Does the oligomeric state of RIG-I change upon RNA binding in or- der to trigger signaling? How is RIG-I regulated by ubiquitin and its E3 ubiquitin ligase TRIM25? The structure of the PRYSPR

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