Modelling the Evolutionary Dynamics of Cheating in Viral Infections

Abstract: Viral replication requires shared gene products that can be used by multiple viral genomes within the same cell. This gives rise to viral ‘cheats’, a type of mutant genome formed by large deletions, that spread by parasitizing full-length viruses. Cheats emerge spontaneously in laboratory infections of almost all known viruses, driving drastic reductions in viral population sizes, and reflecting a fundamental manifestation of conflict in virus evolution. However, our knowledge of viral cheating is limited almost entirely to laboratory studies conducted in tissue culture conditions. Understanding the evolution of viral cheats in natural infections would pave the way for transformative new ways to predict and control viral infections. In our previous working group on this topic, we developed a model for the within-host population dynamics of viral cheats. We used birth-death dynamics, and explicitly modelled the changes in the abundance of viral deletions of varying lengths over the course of an acute influenza infection. This model structure now allows us to advance two key goals: to explore the qualitative features of viruses in which cheats can drive population extinction; and to infer quantitatively the selective advantage of cheating using sequencing data from natural viral infections.