Endogenous retroviruses: acquisition, amplification and taming of genome invaders

•Endogenous retroviruses as remnants of ancestral germline infections.•Ongoing endogenisation of infectious retroviruses reported in some mammals.•Possible evolution towards an intracellular replicative cycle.•Multiple mechanisms controlling the activity of these elements in vivo.

Endogenous retroviruses are interspersed genomic elements that were generated after infectious retroviruses entered the germline of their host. They were initially identified as degenerate remnants of past infections, but new models of very recent or ongoing endogenisation are now emerging, allowing the real time investigation of the first steps of the coexistence between these elements and their host. Domestication of endogenous retroviruses involves several mechanisms, including transcriptional control of these elements and regulation of their mobility through the action of restriction factors. Recent studies also point towards an until-now unexpected role of the immune system for the control of these elements, even those that do not contain fully infectious copies.