Human Endogenous Retroviruses and the Placenta

Up to 8% of the human genome is of retroviral origin. These stably integrated retroviral sequences that characterize the human endogenous retrovirus (HERV) arose from retroviral infections that occurred more than 25 million years ago. The host and the retrovirus have subsequently coevolved as retrovirally derived genetic material is propagated in a Mendelian fashion. Although most HERV sequences are silenced, several have been described that are functional. The effects of some HERV-derived products are linked to human disease; others appear essential to human organ function. The human placenta, unique in its active expression of retroviral sequences that are not expressed in other tissues, may hold the key to an improved understanding of the functional significance of HERVs. In this review, we discuss the contribution of retroelements, particularly HERVs, to placental function and dysfunction. We describe fusogenic and immunosuppressive HERV activities and emphasize epigenetic regulation of retroelement expression.