Descripción del proyecto
Un nuevo método para controlar las infecciones víricas
Los brotes víricos necesitan una primera línea de estrategias antivíricas, ya que el desarrollo de vacunas o tratamientos con anticuerpos previa solicitud no es siempre viable. El proyecto financiado con fondos europeos LOFlu investigará las interacciones hospedador-patógeno en la infección por el virus de la gripe A (VGA). Se prestará especial atención a las inclusiones víricas con propiedades líquidas que se forman durante el ensamblaje vírico y constituyen un paso clave en el ciclo de vida del virus. Mediante el estudio de cómo el hospedador y el virus trabajan en armonía para coordinar la formación y las propiedades materiales de las inclusiones líquidas del VGA y sus interacciones, los investigadores arrojarán luz sobre la organización de las reacciones víricas en el tiempo y el espacio, así como sobre los principios que rigen el ensamblaje de los genomas epidémicos y pandémicos del VGA.
Objetivo
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.
Ámbito científico
- 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
Palabras clave
Programa(s)
Régimen de financiación
ERC-COG - Consolidator GrantInstitución de acogida
1067-001 LISBOA
Portugal