This NSF RAPID project supports the development of an experimental and computational platform that allows researchers to examine how the Ebola virus genome evolves or changes with time and as it moves from bat to human hosts. The Ebola virus is an RNA virus. Like other RNA viruses, it exists as a diverse collection of related, but distinct individual viruses. It is thought that this diversity allows the virus to adapt to environmental changes. The deep sequencing of a virus population as it evolves in human and bat cells will allow for a better understanding viral evolution and identify factors that facilitate adaptation and lead to spread and disease. Understanding virus evolution will better enable researchers to control future Ebola virus outbreaks and develop better vaccines for its prevention.

The extreme capacity of RNA viruses for rapid evolution is emerging as one of the key determinants of pathogenicity and virulence, as well as the driving force underlying the rapid emergence of new viral strains and the development of resistance to antivirals. Despite its importance, few conceptual and experimental tools are currently available to study viral evolution and its relationship to pathogenesis. In this RAPID award, the PI proposes to examine Ebola virus evolution and its relationship to replication in human and bat cells. The approach will combine virological experiments, novel genome analysis approaches and computational modeling to uncover basic principles of Ebola virus evolution. The investigators will address fundamental questions about the rules that govern Ebola cycling between human and bats including: 1) what determines the diversity of the virus population: the rate of generation of mutations or the selective pressures on the virus population? 2) what are the potential genetic structures adapted by a given virus population under different environments and how dynamic are these structures under diverse environmental conditions? 3) What is the relationship between viral quasispecies diversity, fitness and adaptability? The results from these experiments will open the way to understand how the evolution of Ebola virus populations determines the outcome of infection. These approaches will have a major impact in vaccine development, on the ability to anticipate and control Ebola virus outbreaks, and on the understanding of rapid evolution of RNA genomes.