Molecular and functional genomics of ancient viral epidemics
- Lucie Etienne, CIRI, Centre International de Recherche en Infectiologie, Université Lyon 1 - ENS de Lyon
- David Enard, Ecology and Evolutionary Biology, UArizona
Bats (Chiroptera) are one of the most diverse mammalian order. They host many viruses, including modern-day high-profile zoonoses (rabies, Nipah, Ebola & Marburg filoviruses, SARS coronavirus) and viruses close to primate pathogens (poxvirus, Hepatitis B Virus). Bats appear relatively asymptomatic to viral infections that are pathogenic to most mammals. The potential causes are their life-history traits, physiology, and unique immune features. However, most evolutionary history and mechanisms of bat-virus interactions are still unknown. Furthermore, past arms-races have only been studied on a limited number of host antiviral factors or viral receptors, or on a large scale but without functional evidence. The project proposes to turn to the past to apprehend the future better to unravel the true scale and the functional evolutionary mechanisms of the long-term battle between bats and viruses: by detecting ancient epidemics through bat genomic adaptation and molecular virology to identify virus families with a pathogenic potential and to unravel innovation in bat genomes that may be key for antiviral prevention/therapeutics.
While the grand challenge is to reveal the true scale and functional mechanisms of virus-driven host adaptation in bats, the specific goal of this project is to identify and functionally characterize ancient viral epidemics in the Myotis bat genus, through the lens of Myotis bats genomic and functional adaptation. The project team is structured in way that creates a positive feedback loop: (i) Etienne’s team provides the ability to functionally dissect virus-driven genomic adaptations detected by Enard’s team, and (ii) Enard’s team analyzes the genome-wide extent of past viral epidemics suggested by gene candidate evidence from Etienne’s. The PhD students will focus on Myotis bats that have ideal divergence for the study of genomic adaptation and for which we have novel genomes, cell lines, and genetic manipulation and virology tools.
The collaboration is meant to fill a critical and increasingly problematic gap in the study of the evolution of host-virus interactions. Even though the collaboration is new the synergy between the two teams is exciting. They naturally work in a reciprocal manner: The Enard student will teach the molecular evolution and populations genetics principles and tools to the Etienne-student. The Etienne-student will teach molecular techniques to the Enard-student during yearly winter visits (when Myotis hibernate). This synergy will ensure that the future generation of researchers working on virus-driven host adaptation can start labs that will unite all the skills and abilities currently present in separate labs in separate countries.