Paleovirology of bornaviruses: What can be learned from molecular fossils of bornaviruses.

Endogenous viral elements (EVEs) are virus-derived sequences embedded in eukaryotic genomes formed by germline integration of viral sequences. As many EVEs were integrated into eukaryotic genomes millions of years ago, EVEs are considered molecular fossils of viruses. EVEs can be valuable informational sources about ancient viruses, including their time scale, geographical distribution, genetic information, and hosts. Although integration of viral sequences is not required for replications of viruses other than retroviruses, many non-retroviral EVEs have been reported to exist in eukaryotes. Investigation of these EVEs has expanded our knowledge regarding virus-host interactions, as well as provided information on ancient viruses. Among them, EVEs derived from bornaviruses, non-retroviral RNA viruses, have been relatively well studied. Bornavirus-derived EVEs are widely distributed in animal genomes, including the human genome, and the history of bornaviruses can be dated back to more than 65 million years. Although there are several reports focusing on the biological significance of bornavirus-derived sequences in mammals, paleovirology of bornaviruses has not yet been well described and summarized. In this paper, we describe what can be learned about bornaviruses from endogenous bornavirus-like elements from the view of paleovirology using published results and our novel data.