Villains or heroes? The raison d'être of viruses

Watanabe, Tokiko; Kawaoka, Yoshihiro

Retroviruses are found in almost all mammals and other vertebrates, and approximately 8% of the human genome is composed of retroviruses in the form of endogenised proviruses. 29, 30 Given that only about 1% of genomic DNA is made up of protein-coding genes, the abundance of retrovirus sequences in the human genome is remarkable. Retrovirus sequences are conserved in humans and other primates, and therefore, the endogenisation of retroviruses is thought to have occurred millions of years ago. 31 Some endogenous retroviruses have been shown to play beneficial roles in their hosts, including host evolution. For example, envelope genes from endogenous retroviruses contribute to the formation of the placenta during the fusion of syncytiotrophoblast cells in mammals. 32, 33 In addition, endogenous retroviral elements are known to protect host cells from infection with exogenous retroviruses in some mammals. [33] [34] [35] In addition to retroviruses, recent studies have shown that non-retroviral viruses have also endogenised in many mammalian species. [36] [37] [38] For example, Tomonaga's group, which is one of the research groups in our Neo-virology research consortium, discovered that bornaviruses, a genus of non-segmented, negative-strand RNA virus, have been endogenised in the genomes of many mammals, including humans. 36 Since bornaviruses do not encode reverse transcriptase and integrase genes, integration of bornavirus segments is believed to be mediated by long interspersed nuclear element-1 (LINE-1), which is a retrotransposon widely distributed in mammalian genomes. 39 Tomonaga's group also showed that an endogenous bornavirus-like element in the ground squirrel genome blocks infection and replication of extant endogenous bornavirus. 40 Together, these findings indicate a potential role for endogenous non-retroviral elements in antiviral defence. This group also performed an evolutionary phylogenetic analysis to elucidate the functions of endogenous bornavirus in mammalian genomes. 41 Thus, it has become apparent that a large number of endogenous viral elements have accumulated in host genomes, more than previously expected. Therefore, it is important that we understand the significance of endogenous viral elements to the biological function and evolution of hosts.