Higher viral virulence accelerates the evolution of host resistance

Parasites and pathogens vary strikingly in their virulence and the resulting selection they impose on their hosts. While the evolution of different virulence levels is well studied, the evolution of host resistance in response to different virulence levels is less understood and as of now mainly based on theoretical predictions. High virulence can increase selection for host resistance evolution if resistance costs are outweighed by the benefits of avoiding infection. To test this, we experimentally evolved the bacterium Vibrio alginolyticus against two variants of the filamentous phage, VALGΦ8, that differ in their virulence. The bacterial host exhibited two alternative defense strategies against future viral infection: (1) super infection exclusion (SIE) whereby viral-infected cells were immune to subsequent infection at a cost of reduced growth, and (2) surface receptor mutations in genes encoding the MSHA type-IV pilus providing resistance to infection by preventing viral binding. While SIE emerged rapidly against both viruses, resistance evolved faster against the high virulence compared to the low virulence virus. Using a mathematical model of our system we show that increasing virulence strengthens selection for resistance due to the higher costs of infection suffered by SIE immune hosts. In both the experiments and the model, higher levels of evolved resistance in the host population drove more rapid virus extinction. Thus, by accelerating the evolution of host resistance, more virulent viruses caused shorter epidemics.