A growing body of evidence indicates that evolutionary interaction with endogenous retroviruses (ERVs) has played a fundamental role in shaping mammalian evolution. For example, ERV-derived proteins and regulatory sequences have been shown to play a pivotal role in mammalian development, and several lines of evidence support a role for ERVs in the antiviral immunity evolution. Intriguingly, viral infection can trigger the expression of otherwise silenced ERV loci, suggesting that ERVs might serve as strategic orchestrators of antiviral defenses.
ERVs are also considered possible drivers of pathological conditions, and it is likely that the loss of balance between the control of ERV expression and its domestication to the host physiology (e.g., in disorders characterized by immune and epigenetics dysregulation) can contribute to complex diseases.
The post-genomic era provides unprecedented possibilities to investigate ERV contribution to mammalian development and physiopathology. Unfortunately, however, ERV research remains fraught with misconceptions and challenged by complications in dealing with highly repetitive sequences.
This Special Issue aims to provide an updated survey of ERV interplay with the host biology, with particular attention to clarifying fundamental misconceptions and controversies regarding the evolutionary origins of ERVs in the human genome and their possible contributions to human evolution and pathogenesis.