The evolutionary dynamics of viruses: virion release strategies, time delays and fitness minima.

Viruses exhibit a diverse array of strategies for infecting host cells and for virion release after replication. Cell exit strategies generally involve either budding from the cell membrane or killing the host cell. The conditions under which either is at a selective advantage is a key question in the evolutionary theory of viruses, with the outcome having potentially important impacts on the course of infection and pathogenicity. Although a plethora of external factors will influence the fitness of either strategy; here, we focus just on the effects of the physical properties of the system. We develop theoretical approaches to assess the effects of the time delays between initial infection and virion release. We show that the length of the delay before apoptosis is an important trait in virus evolutionary dynamics. Our results show that for a fixed time to apoptosis, intermediate delays lead to virus fitness that is lower than short times to apoptosis - leading to an apoptotic strategy - and long times to apoptosis - leading to a budding strategy at the between-cell level. At fitness minima, selection is expected to be disruptive and the potential for adaptive radiation in virus strategies is feasible. Hence, the physical properties of the system are sufficient to explain the existence of both budding and virus-induced apoptosis. The fitness functions presented here provide a formal basis for further work focusing on the evolutionary implications of trade-offs between time delays, intracellular replication and resulting mutation rates.