Cooperative nature of viral replication

The ability of viruses to infect their hosts depends on rapid dissemination following transmission. The notion that viral particles function as independent propagules has been challenged by recent observations suggesting that viral aggregates show enhanced infectivity and faster spread. However, these observations remain poorly understood. Here, we show that viral replication is a cooperative process, such that entry of multiple viral genome copies into the same cell disproportionately increases short-term viral progeny production. This cooperativity arises from the positive feedback established between replication templates and virus-encoded products involved in replication and should be a general feature of viruses. We develop a simple model that captures this effect, verify that cooperativity also emerges in more complex models for specific human viruses, validate our predictions experimentally using different mammalian viruses, and discuss the implications of cooperative replication for viral fitness.