Herpesviral capture of immunomodulatory host genes

Herpesviruses have acquired numerous genes from their hosts. Although these homologs are not essential for viral replication, they often have important immunomodulatory functions that ensure viral persistence in the host. Some of these viral molecules are called virokines as they mimic cellular cytokines of their host such as interleukin-10 (cIL-10). In recent years, many viral homologs of IL-10 (vIL-10s) have been discovered in the genome of members of the order Herpesvirales. For some, gene and protein structure as well as biological activity and potential use in the clinical context have been explored. Besides virokines, herpesviruses have also captured genes encoding membrane-bound host immunomodulatory proteins such as major histocompatibility complex (MHC) molecules. These viral MHC mimics also retain many of the functions of the cellular genes, in particular directly or indirectly modulating the activity of natural killer cells. The mechanisms underlying capture of cellular genes by large DNA viruses are still enigmatic. In this review, we provide an update of the advances in the field of herpesviral gene piracy and discuss possible scenarios that could explain how the gene transfer from host to viral genome was achieved.