Tracking a virus’ next move

Each living organism has a unique place in the tree of life, and, remarkably, viruses pervade every branch, infecting their respective hosts. In this context, host organisms have evolved immune responses such as restriction factors to control infection, and viruses have co-evolved to resist them. This phenomenon repeats over time, and the outcome depends on how quickly and likely viruses and hosts can adapt. The result is the longest battle we have ever witnessed — the arms race between pathogens and hosts. This is why I have always been fascinated to understand this evolutionary race for innovation, and what we can do in the laboratory, as chess masters, to anticipate a pathogen’s next move.

The idea of predicting evolution is a utopian one, as it involves the inherent stochasticity of mutation, reproduction and environment, as well as the unknowns of how genotype dictates phenotype that together determine the fitness landscape. However, we can test in the laboratory the impact of a variety of mutations at the phenotypic level through deep mutational scanning (DMS) approaches. To perform a DMS experiment, each amino acid in a protein is changed to every other possible amino acid and then mutants are tested to study changes in function against a specific selection pressure. The DMS concept was first introduced about a decade ago. Since then, it has been used to study various aspects of protein science, such as protein function, amino acid roles, evolvability, epistasis and more.