Description du projet
Étudier les menaces virales zoonotiques
Les virus des animaux sauvages constituent une réelle menace pour la santé publique, comme en témoignent les épidémies d’Ebola et la pandémie de COVID-19. Cependant, on sait peu de choses sur le fonctionnement de ces virus. Le projet EVADER, financé par l’UE, étudiera l’émergence virale d’un point de vue évolutif. En étudiant comment les mutants de la gamme d’hôtes apparaissent et s’adaptent aux cellules humaines, il fournira le paysage le plus complet de l’infectivité virale des cellules humaines à ce jour. Le projet étudiera également le tropisme cellulaire dépendant du récepteur des virus à ARN enveloppés — un processus expérimentalement traitable impliqué dans l’émergence virale. Enfin, il fournira des indices importants sur le rôle de la mutation spontanée dans l’émergence virale et explorera la faisabilité des thérapies antivirales au niveau du clade.
Objectif
The emergence of new human pathogenic viruses from animal reservoirs is an increasing concern, but also a poorly understood process. Massive sequencing programs have been recently launched to characterize wildlife viruses, but empirical information on how these viruses function and whether they can potentially infect humans is needed. However, the isolation and culturing of wildlife viruses is too often unfeasible due to technical issues, biosafety concerns, or lack of full-length sequence information. Furthermore, we need to investigate viral emergence from an evolutionary standpoint to better understand how host-range mutants appear and adapt to human cells. To achieve these goals, we will focus on the receptor-dependent cell tropism of enveloped RNA viruses, a central and experimentally tractable process involved in viral emergence. First, we will use high-throughput gene synthesis to create hundreds of pseudoviruses coated with the envelopes of previously uncharacterized wildlife viruses belonging to different families, and we will examine their ability to infect a panel of humans cells from various tissues. This will deliver the most comprehensive landscape of viral human cell infectivity to date. Second, we will use experimental evolution, massive parallel sequencing, and site-directed mutagenesis to explore how viral envelopes diversify, undergo cell tropism shifts, and adapt to human cells. This will provide important clues about the role of spontaneous mutation in viral emergence, and may reveal repeatable evolutionary pathways that could help us improve outbreak predictability. Finally, we will use our experimental results to infer candidate cell receptors for wildlife viruses using machine learning, and to explore the feasibility of broad-range, clade-level antiviral therapies that could be used for combating emerging viruses in the future.
Champ scientifique
- medical and health scienceshealth sciencesinfectious diseasesRNA viruses
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesgeneticsmutation
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencescomputer and information sciencesartificial intelligencemachine learning
Programme(s)
Thème(s)
Régime de financement
ERC-ADG - Advanced GrantInstitution d’accueil
46010 Valencia
Espagne