Endogenous retroviruses (ERVs) are remnants of ancient retroviral infections that were integrated into the human genome millions of years ago. They constitute approximately 8% of the human genome. Once considered “Junk DNA” it is now clear that ERVs are dynamic elements engaged in a continuous dialogue with the host innate immune system. This review further advances our current understanding of how ERV expression interfaces with innate immune signalling by providing insights into the dual nature of this interaction: (i) how the accidental detection of ERV-derived nucleic acids and proteins by pattern recognition receptors (PRRs), such as cGAS, RIG-I, and TLRs, can trigger protective interferon responses and inflammation, and (ii) the key innate immune regulatory mechanisms that suppress or control ERV activity, maintaining genomic stability. Furthermore, the study also sheds light on this balance for maintaining cellular homeostasis, providing the idea of how the disruption of this balance leads to the pathogenesis of autoimmune diseases, cancer, and neurological disorders, consequently unlocking therapeutic innovations.
Iftikhar et al. (Fri,) studied this question.