Ecological and evolutionary dynamics of cell-virus-virophage systems

Abstract

Microbial eukaryotes can be infected by giant viruses, which can be infected by virophages. Virophages are parasites of the virus transcription machinery and can interfere with virus replication, resulting in a benefit to the eukaryotic host population. Surprisingly, virophages can integrate into the genomes of their cell or virus hosts, and have been shown to reactivate during coinfection. This raises interesting questions about the role of integration in the dynamics of cell-virus-virophage systems. Here, we use mathematical models and computational simulations to understand the effect of virophage integration on populations of cells and viruses. We also investigate programmed-cell death (PCD) and multicellularity as potential antiviral defence strategies used by cells. We found that virophages which enter the cell independently of the host virus, such as Mavirus, are expected to integrate commonly into the genomes of their cell hosts. In contrast, we show that virophages like Sputnik which form a complex with the giant virus, should rarely be found integrated in cell genomes. Alternatively, we found that Sputnik virophages can stably persist integrated in the virus population, as long as they do not completely inhibit virus replication. We also show that increasing virophage inhibition can stabilise oscillatory dynamics, which may explain the long-term persistence of viruses and virophages in the environment. Our results demonstrate that inhibition by virophages, PCD and multicellularity are effective antiviral strategies that may act in synergy against viral infection in microbial species.