Description du projet
Une nouvelle approche pour contrôler l’infection virale
Les épidémies virales nécessitent une première ligne de stratégies antivirales étant donné que le développement à la demande de vaccins ou de traitements par anticorps n’est pas toujours possible. Le projet LOFlu, financé par l’UE, examinera les interactions hôte-agent pathogène dans l’infection au virus de la grippe A (VGA). Une attention particulière sera portée aux inclusions virales dotées de propriétés liquides qui se forment durant l’assemblage viral et constituent une étape essentielle du cycle de vie du virus. En étudiant la manière dont l’hôte et le virus travaillent de concert pour coordonner la formation et les propriétés matérielles des inclusions liquides du VGA et leurs interactions, les chercheurs apporteront un éclairage sur l’organisation des réactions virales dans l’espace et le temps, ainsi que sur les principes régissant l’assemblage des génomes du VGA épidémique et pandémique.
Objectif
The world health organization monitors viral infections worldwide with the aim to coordinate strategies to control viral outbreaks. The on-demand development of vaccines or antibody treatment does not confer a first line of defense against unpredictable infections caused by new viruses in humans such as pandemic influenza, corona or Ebola viruses, and new approaches are needed. We propose to investigate the fundamental basis of novel host-pathogen interactions in influenza A virus (IAV) infection that may define new antiviral strategies. We discovered that the important pathogen IAV induces the intracellular assembly of viral inclusions that behave like liquid organelles. IAV inclusions serve as assembly sites for the IAV segmented genome, a key step in the viral lifecycle. We now find that the maintenance of the liquid character of IAV inclusions is essential for viral replication. As we identified some of the host and viral components of IAV inclusions, we now have the tools to interrogate how specific interactions and cellular processes result in phase-separated compartments. We aim to learn how the function of IAV inclusions is related to their material state and investigate the potential of imposing phase transitions in an organism to limit IAV infection. Phase separation provides a novel conceptual framework to tackle how viruses exploit cells to organize viral reactions in space and in time. It also provides alternative principles for exploring aspects of the IAV lifecycle not yet fully understood, including how influenza epidemic and pandemic genomes assemble. Taken together, we propose a new, integrated approach for studying phase separated phenomena, from the molecular to the organismal level, that will bring a deeper understanding and control to viral infections. Our work will also be of relevance to other fields of biomedicine, including in the science of soft matter that is involved in neurodegenerative diseases and some cancers.
Champ scientifique
- natural sciencesbiological sciencesmicrobiologyvirology
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesebola
- medical and health scienceshealth sciencespublic healthepidemiologypandemics
- medical and health scienceshealth sciencesinfectious diseasesRNA virusesinfluenza
- natural sciencesbiological sciencesgeneticsgenomes
Mots‑clés
Programme(s)
Régime de financement
ERC-COG - Consolidator GrantInstitution d’accueil
1067-001 LISBOA
Portugal