Linking Virus Population Genetic Structure to Infectivity and Adaptation

Investigator: Raul Andino-Pavlovsky, PhD
Sponsor: DOD Defense Advanced Projects Research Agency

Location(s): United States


United States Department of Defense, Defense Advanced Research Projects Agency (DARPA) project titled, “Linking Virus Population Genetic Structure to Infectivity and Adaptation:” collaboration with the University of California, San Francisco and Stanford University (CA); Mount Sinai School of Medicine (NY); Leloir Institute (Argentina); and SAIC Inc. (San Diego, CA).

The project focuses on dengue virus (DENV) with a goal to examine cross-species adaptation on the natural virus cycle from mosquito to mammalian cells. DENV offers a unique opportunity to capture how the quasispecies structure and dynamics determine cycling between insect and human environments. The objective is to predict viral evolutionary trajectories and pathogenic potential.

The study is focused on diversity and sequence structure of a viral population and how these features are associated with fitness. A new accurate approach to measure the mutation distribution of viral quasispecies (i.e. the genetic structure of the population) was developed, and this information is linked to experimentally measured viral fitness landscapes through developed computer algorithms.

The fundamental force shaping virus evolution is its interaction with the host machinery, whereby for example the cellular environment modulate viral diversity and immune mechanisms acts as constant selective pressures. The computational task is to identify these forces via analysis and integration of heterogeneous omics data: NGS sequencing, mass-spec proteomics, image analysis, etc. The wider goal is to predict the ability of any RNA virus to jump from other species into humans, spread in the human population and cause disease.