Endogenous viruses: insights into viral evolution and impact on host biology

• Published in: Nature reviews. Genetics Vol. 13; no. 4; pp. 283 - 296
• Main Authors: Feschotte, Cédric, Gilbert, Clément
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.04.2012; Nature Publishing Group
• Subjects: 631/208/325/2483; 631/326/596/2554; Agriculture; Animal Genetics and Genomics; Binding Sites; Biodiversity and Ecology; Biological and medical sciences; Biological Evolution; Biology; Biomedical and Life Sciences; Biomedicine; Cancer Research; DNA; DNA, Viral - genetics; Environmental Sciences; Eukaryota - virology; Evolution; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Gene Function; Gene Rearrangement; Genes, Viral; Genetic aspects; Genetics of eukaryotes. Biological and molecular evolution; Genomes; Health aspects; Host-Pathogen Interactions - genetics; Human Genetics; Mosquitoes; Mutagenesis; Mutation; Parasites; Physiological aspects; Promoter Regions, Genetic; Retrovirus; review-article; Transcription Factors - genetics; Transcription Factors - metabolism; Virus Physiological Phenomena; Viruses; Viruses - genetics; France; United States; Virus; Molecular evolution; Endogenous; Review
• ISSN: 1471-0056; 1471-0064
• DOI: 10.1038/nrg3199

Key Points Recent studies have shown that in addition to vertebrate retroviruses, virtually all types of eukaryotic viruses can be endogenized: that is, they can be integrated into the germline genome of their host and vertically inherited. The endogenization of non-retroviral viruses is believed to result from accidental integration mediated by various mechanisms that are encoded either by the viral genome or by the host genome, such as DNA repair processes or resident retrotransposons. Various endogenous viral elements (EVEs) have been dated, showing that the roots of several notorious viral families that are currently circulating in human and animal populations are much deeper than previously thought. Long-term viral substitution rates estimated using the age of EVEs as a calibration point are several orders of magnitude slower than short-term viral substitution rates calculated through comparison of modern viral sequences. The integration of EVEs in the host genome is an important source of structural variation, and EVEs can continue long after integration to provoke genomic rearrangements, some of which have been linked to cancer and other diseases. Recent genome-wide studies have shown that thousands of mammalian endogenous retroviral sequences have been co-opted to control host gene expression, substantially contributing to regulatory innovation in mammals. The domestication of EVE protein-coding sequences has led to the birth of new host genes, most of which are used to combat exogenous viruses or for the physiology and development of the placenta. A large array of viral sequences is being uncovered in eukaryotic genome sequences, revealing that almost any type of virus — not just retroviruses — can become part of host genomes. These discoveries provide new information about the origins and evolution of modern day viruses and host–virus relationships. Recent studies have uncovered myriad viral sequences that are integrated or 'endogenized' in the genomes of various eukaryotes. Surprisingly, it appears that not just retroviruses but almost all types of viruses can become endogenous. We review how these genomic 'fossils' offer fresh insights into the origin, evolutionary dynamics and structural evolution of viruses, which are giving rise to the burgeoning field of palaeovirology. We also examine the multitude of ways through which endogenous viruses have influenced, for better or worse, the biology of their hosts. We argue that the conflict between hosts and viruses has led to the invention and diversification of molecular arsenals, which, in turn, promote the cellular co-option of endogenous viruses.