Endogenous Retroviruses: With Us and against Us.

Thomas J. Meyer,Jimi L. Rosenkrantz,Shawn L. Chavez,Lucia Carbone

doi:10.3389/fchem.2017.00023

Abstract

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.

Highlights

A retroviral genome exists in different forms during its replication cycle
Elevated endogenous retroviruses (ERVs)-K (HML-2) activity has been observed in the brain tissue of amyotrophic lateral sclerosis (ALS) patients (Douville et al, 2011), while transgenic animals expressing the ERV-K env gene in cortical and spinal neurons developed motor dysfunction, suggesting that these elements may contribute to neurodegeneration (Li et al, 2015)
ERVs are known to be involved in disease through insertional mutagenesis, as targets of epigenetic repression, and via recombination of sequences between the homologous copies of these elements scattered across the genome

Summary

Introduction

A retroviral genome exists in different forms during its replication cycle. A viral particle, or virion, protects the RNA genome of the retrovirus during escape from the host cell and infection of new cells. ERVs activity is associated with a number of human diseases and the target of epigenetic repression by the host genome. Given that some ERV families have expanded substantially in the number of genomic integrations in animals (Tristem, 2000; Bénit et al, 2001), it has been hypothesized that widespread reactivation of ERVs during the waves of global reprogramming within germ cell and pre-implantation development are largely responsible for this expansion.

Results

Conclusion