Final Report Summary - RNAVIRUSPOPDIVNVAX (RNA virus population diversity, virulence, attenuation and vaccine development.)
In attempts to better characterize these viral populations, we developed deep sequencing and computational approaches that permit unprecedented resolution in identifying and monitoring the genetic changes occurring within viral populations, that had previously remained undetectable by more classic sequencing technologies. Using these new tools, we were able to describe how a virus population is able to adapt to a new growth condition, through the contribution of several minority variants interacting with the majority genotype. We have also characterized how viruses are able to jump to new hosts, and replicate between a set of well defined hosts. Finally, by applying our approaches to monitor the evolution of a virus in vivo, we were able to identify how a virus navigates through a host to survive genetic bottlenecks, and how monitoring viruses in the subpopulations at transmission sites can be used to predict future emergence events.
In addition to this strictly fundamental research, the expertise we acquired has permitted us to develop new antiviral approaches. Fidelity variants are now being seriously explored as methods of generating safer and more stable live attenuated vaccines (high-fidelity variants) or more diverse vaccine seeds that present broader antigenic diversity (low-fidelity variants). Fidelity variants have also proven to be good tools to identify new compounds with antiviral, mutagenic activity. Finally, by altering a virus' ability to generate mutation, or altering its ability to survive mutation, we have developed to methods of attenuating virulent strains, to create new vaccine strains.