  RNA viruses exist as genetically diverse populations displaying different
phenotypes, including diverse degrees of virulence. The evolution of virulence
in viral populations is, however, poorly understood. Based on the experimental
observation of an RNA virus clone in cell culture diversifying into two
subpopulations of different virulence, we study the dynamics of heterogeneous
virus populations and the evolution of virulence. We introduce a
competition-colonization trade-off into standard mathematical models of
intra-host viral infection. Colonizers are fast spreading, virulent strains,
whereas competitors are less virulent variants that are more successful within
coinfected cells. We observe biphasic dynamics of the population: Early in the
infection the population is dominated by colonizers, which later will be
outcompeted by competitors. The simulations suggest the existence of a steady
state where few low-virulence variants coexist. This equilibrium implies
collective virulence attenuation in the population, in contrast to previous
models predicting development of the population towards increased virulence.
Nevertheless, the attenuation effect disappears if we include a highly
simplified immune response in our models. Thus, the competition-colonization
trade-off indicates a role for virulence in the modulation of the viral
population diversity. The evolution of virulence is a dynamic feature of the
population shaped by interactions between individuals and by the structure of
the patchy habitat.
