Endogenous Retroelements and the Host Innate Immune Sensors

The ability to distinguish between self and nonself is the fundamental basis of the immune system in all organisms. The conceptual distinction between self and nonself, however, breaks down when it comes to endogenous retroviruses and other retroelements. While some retroelements retain the virus-like features including the capacity to replicate and reinvade the host genome, most have become inactive through mutations or host epigenetic silencing. And yet, accumulating evidence suggests that endogenous retroelements, both active and inactive, play important roles not only in pathogenesis of immune disorders, but also in proper functioning of the immune system. This review discusses the recent development in our understanding of the interaction between retroelements and the host innate immune system. In particular, it focuses on the impact of retroelement transcripts on the viral RNA sensors such as Toll-like receptors, RIG-I-like receptors, protein kinase R, and the inflammasomes.