Projektbeschreibung
Forschung zur Übertragung von Virusinfektionen vom Tier auf den Menschen
Viren, die von Wildtieren auf den Menschen übertragen werden, sind ein großes Gesundheitsrisiko, wie die Ebola- und COVID-19-Pandemien verdeutlichten. Allerdings ist die Funktionsweise solcher Viren noch kaum erforscht. Schwerpunkt des EU-finanzierten Projekts EVADER ist nun die evolutionäre Entwicklung dieser Viren. Analysen zur Entstehung wirtsspezifischer Mutanten und der Anpassung an menschliche Zellen sollen die bislang genaueste Übersicht über die virale Infektiösität im Zusammenhang mit menschlichen Zellen liefern. Das Projekt untersucht zudem den rezeptorabhängigen Zelltropismus behüllter RNA-Viren – einen für die Virusevolution bedeutsamen und experimentell nachstellbaren Mechanismus. Schließlich wird es wichtige Belege liefern, wie Spontanmutationen zur Virusevolution beitragen, und auf systematischer Ebene (Klade) an antiviralen Medikamenten forschen.
Ziel
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.
Wissenschaftliches Gebiet
- medical and health scienceshealth sciencesinfectious diseasesRNA viruses
- natural sciencesbiological sciencesmicrobiologyvirology
- natural sciencesbiological sciencesgeneticsmutation
- natural sciencesbiological sciencesgeneticsRNA
- natural sciencescomputer and information sciencesartificial intelligencemachine learning
Programm/Programme
Thema/Themen
Finanzierungsplan
ERC-ADG - Advanced GrantGastgebende Einrichtung
46010 Valencia
Spanien