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Front Chem. 2017 Apr 7;5:23. doi: 10.3389/fchem.2017.00023. eCollection 2017.

Endogenous Retroviruses: With Us and against Us.

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Division of Bioinformatics and Computational Biology, Department of Medical Informatics and Clinical Epidemiology, Oregon Health & Science UniversityPortland, OR, USA.
Department of Molecular and Medical Genetics, Oregon Health & Science UniversityPortland, OR, USA.
Division of Reproductive & Developmental Sciences, Oregon National Primate Research CenterPortland, OR, USA.
Department of Medicine, Knight Cardiovascular Institute, Oregon Health & Science UniversityPortland, OR, USA.
Departments of Obstetrics and Gynecology and Physiology and Pharmacology, Oregon Health & Science University School of MedicinePortland, OR, USA.


Mammalian genomes are scattered with thousands of copies of endogenous retroviruses (ERVs), mobile genetic elements that are relics of ancient retroviral infections. After inserting copies into the germ line of a host, most ERVs accumulate mutations that prevent the normal assembly of infectious viral particles, becoming trapped in host genomes and unable to leave to infect other cells. While most copies of ERVs are inactive, some are transcribed and encode the proteins needed to generate new insertions at novel loci. In some cases, old copies are removed via recombination and other mechanisms. This creates a shifting landscape of ERV copies within host genomes. New insertions can disrupt normal expression of nearby genes via directly inserting into key regulatory elements or by containing regulatory motifs within their sequences. Further, the transcriptional silencing of ERVs via epigenetic modification may result in changes to the epigenetic regulation of adjacent genes. In these ways, ERVs can be potent sources of regulatory disruption as well as genetic innovation. Here, we provide a brief review of the association between ERVs and gene expression, especially as observed in pre-implantation development and placentation. Moreover, we will describe how disruption of the regulated mechanisms of ERVs may impact somatic tissues, mostly in the context of human disease, including cancer, neurodegenerative disorders, and schizophrenia. Lastly, we discuss the recent discovery that some ERVs may have been pressed into the service of their host genomes to aid in the innate immune response to exogenous viral infections.


endogenous retrovirus; genome; human disease; innate immunity; placenta; pre-implantation embryo; stem cells

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