Intra-host versus inter-host selection: viral strategies of immune function impairment.

We investigate the evolution of viral strategies to counteract immunological attack. These strategies can be divided into two classes: those that impair the immune response inside or at the surface of a virus-infected cell and those that impair the immune response outside an infected cell. The former strategies confer a "selfish" individual selective advantage for intra-host competition among viruses. The latter strategies confer an "unselfish" selective advantage to the virus population as a group. A mutant, defective in the gene coding for the extracellular immune function-impairment strategy, may be protected from immune attack because the wild-type virus in the same host successfully impairs the host's immune function. Such "unselfish" defense strategies are neutral with respect to intra-host competition. We present simple models of viral intra-host and combined inter- and intra-host evolution. We show that selfish strategies can evolve by intra-host evolution. Unselfish strategies may evolve if inter-host selection pressures outweigh intra-host selection, suggesting that such strategies can only evolve in viruses with low mutation rates.