Endogenous retroviruses and the development of cancer

Abstract

Mammalian genomes include a considerable number of endogenous retroviruses (ERVs), relics of ancestral infectious retroviruses, whose proviruses have invaded the germ-line. The documented ability of infectious retroviruses to cause cancer has greatly contributed to the discovery of ERVs. It also reinforced the concept that ERVs are causative agents of many cancers, a notion that historically has not always stood up to experimental scrutiny. The recent greater appreciation of the complexity of ERV biology and the identification of dedicated host mechanisms controlling ERV activity have revealed novel interactions between ERVs and their hosts, with the potential to cause or contribute to disease. In this review, the involvement of ERVs in cancer initiation and progression is discussed, as well as their contribution to our understanding of the process of transformation and to the invention of innovative preventive and therapeutic cancer treatments.

Figure 1. Retroelement composition of the mouse genome.

The proportion of LTR retroelements (MaLRs and ERVs) and non-LTR retrotransposons (LINEs and SINEs) is depicted. The typical genomic structure of distinct ERVs, adopted from (91), is also shown. ORF overlap has been removed for simplicity.

Figure 2. Potential mechanisms of ERV-mediated transformation.

Non-allelic homologous recombination between ERVs creates chromosomal rearrangements. New ERV integrations may disrupt a host gene. ERV transcriptional derepression can activate downstream genes. Accumulated incomplete ERV replication intermediates activate innate immunity or disregulate non-coding RNA networks. Certain retroviral proteins (e.g. envelope) mediate immunosuppression and may also be involved in cellular fusion.