Role of Endogenous Retroviruses in Human Genetic Diseases

Abstract

It is now increasingly realised that many repetitive elements such as endogenous retroviruses (ERVs), remnants of ancient retroviral infections, can contribute to the host's genetic and transcriptional identity in complex ways. There is growing evidence that specific ERVs are not genomic ‘junk’, but have biological significance in humans. Some ERVs have been ‘co‐opted’ for human biological processes, and the nucleic acids and proteins of these ERVs are able to modify human gene expression and regulatory networks in a cell and tissue‐specific manner, with implications for healthy development, immune function and susceptibility to diseases. Ongoing research explores the possibility that aberrant expression of HERVs would contribute to the pathogenesis of a number of inflammatory disorders, including cancers, multiple sclerosis, amyotrophic lateral sclerosis and schizophrenia. Key Concepts Some HERVs have been ‘co‐opted’ for human biological processes such as placentogenesis, innate immunity pathways, anticancer mechanisms and central nervous system function. ERVs provide a genetic reservoir for promoters, transcription start sites, enhancers and alternative splice donors and acceptors for regulating host gene expression. HERV‐K (HML‐2), the youngest HERV in the human genome, is polymorphic in the human population, meaning that not everyone has the same HERV integration at the same chromosomal position. Np9 and Rec, accessory proteins encoded by HERV‐K (HML‐2), are associated with specific human cancers in several ways: their expression is upregulated, they interact with specific cancer biomarkers and they impact signalling pathways that are implicated with cancer. Specific HERV LTRs help regulate the innate immune response by acting as a reservoir of interferon‐inducible enhancers. HERV transcripts play a role in priming and activating B‐cell responses in a T‐cell‐independent pathway against specific pathogens. Ongoing research explores the possibility that aberrant expression of HERVs would contribute to the pathogenesis of a number of inflammatory disorders, including cancers, multiple sclerosis, amyotrophic lateral sclerosis and schizophrenia.