Human Endogenous Retroviruses: Role in Human Genome Evolution, Implications in Disease, and Potential for Therapeutics

About 8% of the human genome is retroviral in origin. These sequences are thought to be remnants of infections that occurred over millions of years, resulting in the integration of provirus genomes into the DNA of germline cells. Most of these human endogenous retroviruses (HERVs) are defective, containing nonsense mutations or major deletions due to selective pressure against functioning viruses. However, certain HERV proteins can be expressed and some even produce viable virions. Sections of the sequences encoding these HERVs act as promoters and enhancers for human genes. This alters the transcriptome and influences the tissue-specific expression of some genes. HERVs have also been implicated in disease, not only as contributors to pathogenesis but also in a clinical setting, both as biomarkers and as putative targets for treatment or vaccine development. Specifically, upregulated HERV envelope glycoproteins have been shown to promote DNA damage in amyotrophic lateral sclerosis (ALS) cases. In the last few years, HERVs have been associated with many different autoimmune and infectious diseases, and unraveling their role in pathogenesis could provide key insights into future treatments. Since so few HERVs are able to produce viable gene products but have been implicated in a wide range of diseases, research into the mechanism of action of these proteins and possible therapeutics against them may represent an untapped goldmine of research.