Emerging roles for endogenous retroviruses in immune epigenetic regulation*

In recent years, there has been significant progress toward understanding the transcriptional networks underlying mammalian immune responses, fueled by advances in regulatory genomic technologies. Epigenomic studies profiling immune cells have generated detailed genome-wide maps of regulatory elements that will be key to deciphering the regulatory networks underlying cellular immune responses and autoimmune disorders. Unbiased analyses of these genomic maps have uncovered endogenous retroviruses as an unexpected ally in the regulation of human immune systems. Despite their parasitic origins, studies are finding an increasing number of examples of retroviral sequences having been co-opted for beneficial immune function and regulation by the host cell. Here, we review how endogenous retroviruses have given rise to numerous regulatory elements that shape the epigenetic landscape of host immune responses. We will discuss the implications of these elements on the function, dysfunction, and evolution of innate immunity.