Descrizione del progetto
Un nuovo approccio per il controllo dell’infezione virale
Le epidemie virali richiedono strategie antivirali in prima linea poiché lo sviluppo su richiesta di vaccini o di trattamento anticorpale non sempre si rivela valido. Il progetto LOFlu, finanziato dall’UE, studierà le interazioni ospite-patogeno nell’infezione del virus dell’influenza A. Sarà posta particolare attenzione alle inclusioni virali con proprietà fluide che si creano durante l’assemblaggio virale e che costituiscono un passaggio chiave nel ciclo vitale del virus. I ricercatori, studiando il modo in cui ospite e virus lavorano di concerto per coordinare la formazione e le proprietà dei materiali delle inclusioni fluide del virus dell’influenza A e le loro interazioni, faranno luce sull’organizzazione delle reazioni virali nel tempo e nello spazio, oltre che sui principi che regolano l’assemblaggio dei genomi epidemici e pandemici di tale virus.
Obiettivo
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.
Campo scientifico
- 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
Parole chiave
Programma(i)
Argomento(i)
Meccanismo di finanziamento
ERC-COG - Consolidator GrantIstituzione ospitante
1067-001 LISBOA
Portogallo