The role of spatial heterogeneity in the evolution of local and global infections of viruses

Viruses have two modes spread in a host body, one is to release infectious particles from infected cells (global infection) and the other is to infect directly from an infected cell to an adjacent cell (local infection). Since the mode of spread affects the evolution of life history traits, such as virulence, it is important to reveal what level of global and local infection is selected. Previous studies of the evolution of global and local infection have paid little attention to its dependency on the measures of spatial configuration. Here we show the evolutionarily stable proportion of global and local infection, and how it depends on the distribution of target cells. Using an epidemic model on a regular lattice, we consider the infection dynamics by pair approximation and check the evolutionarily stable strategy. We also conduct the Monte-Carlo simulation to observe evolutionary dynamics. We show that a higher local infection is selected as target cells become clustered. Surprisingly, the selected strategy depends not only on the degree of clustering but also the abundance of target cells per se.Author summary: Viruses such as human immunodeficiency virus and measles virus can spread through physical contact between infected and susceptible cells (cell-to-cell infection), as well as normal cell-free infection through virions. Some experimental evidences support the possibility that high ability of cell-to-cell infection is selected in the host. Since the mode of spread affects the evolution of life history traits, it is important to reveal what condition favors high ability of cell-to-cell infection. Here we address what level of cell-to-cell infection is selected in different target cell distributions. Analysis of ordinary differential equations that keep track of dynamics for spatial configuration of infected cells and the Monte-Carlo simulations show that higher proportion of local infection is selected as target cells become clustered. The selected strategy depends not only on the degree of clustering but also the abundance of target cells per se. Our results suggest viruses have more chances to evolve the ability of local infection in a host body than previously thought. In particular, this may explain the emergence of measles virus strains that gained the ability to infect the central nervous system.