IL-10 encoded by viruses: a remarkable example of independent acquisition of a cellular gene by viruses and its subsequent evolution in the viral genome

Many viruses have evolved strategies to deregulate the host immune system. These strategies include mechanisms to subvert or recruit the host cytokine network. IL-10 is a pleiotropic cytokine that has both immunostimulatory and immunosuppressive properties. However, its key features relate mainly to its capacity to exert potent immunosuppressive effects. Several viruses have been shown to upregulate the expression of cellular IL-10 (cIL-10) with, in some cases, enhancement of infection by suppression of immune functions. Other viruses encode functional orthologues of cIL-10, called viral IL-10s (vIL-10s). The present review is devoted to these virokines. To date, vIL-10 orthologues have been reported for 12 members of the family Herpesviridae, two members of the family Alloherpesviridae and seven members of the family Poxviridae. Study of vIL-10s demonstrated several interesting aspects on the origin and the evolution of these viral genes, e.g. the existence of multiple (potentially up to nine) independent gene acquisition events at different times during evolution, viral gene acquisition resulting from recombination with cellular genomic DNA or cDNA derived from cellular mRNA and the evolution of cellular sequence in the viral genome to restrict the biological activities of the viral orthologues to those beneficial for the virus life cycle. Here, various aspects of the vIL-10s described to date are reviewed, including their genetic organization, protein structure, origin, evolution, biological properties and potential in applied research.