Comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes

Abstract

Bornaviruses are the only animal RNA viruses that establish a persistent infection in their host cell nucleus. Studies of bornaviruses have provided unique information about viral replication strategies and virus–host interactions. Although bornaviruses do not integrate into the host genome during their replication cycle, we and others have recently reported that there are DNA sequences derived from the mRNAs of ancient bornaviruses in the genomes of vertebrates, including humans, and these have been designated endogenous borna-like (EBL) elements. Therefore, bornaviruses have been interacting with their hosts as driving forces in the evolution of host genomes in a previously unexpected way. Studies of EBL elements have provided new models for virology, evolutionary biology and general cell biology. In this review, we summarize the data on EBL elements including what we have newly identified in eukaryotes genomes, and discuss the biological significance of EBL elements, with a focus on EBL nucleoprotein elements in mammalian genomes. Surprisingly, EBL elements were detected in the genomes of invertebrates, suggesting that the host range of bornaviruses may be much wider than previously thought. We also review our new data on non-retroviral integration of Borna disease virus.

Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

“…In addition to a nucleoprotein, the genome of bornaviruses encodes five other proteins (a phosphoprotein, a matrix protein, a glycoprotein, an RNA-dependent RNA polymerase and an accessory protein). Several endogenous fragments of the matrix, RNApolymerase and glycoprotein genes have been discovered in the genomes of a number of other vertebrate species [1,12,28,44]. Most endogenous bornaviruses reported to date correspond to the nucleoprotein, which may be owing to the existence of a 3 0 -5 0 transcription gradient of bornavirus genomes, resulting in a higher abundance of nucleoprotein mRNA [28].…”

“…Hepadnaviruses, bornaviruses and circoviruses, however, have not been reported in this group, with the exception of one transcript of a truncated bornavirus nucleoprotein gene (94 aa) found in a Gaboon viper transcriptome [44] and a TBLASTN hit corresponding to our python EBLN3 reported in a supplementary table of Horie et al [28]. In fact, bornaviruses and hepadnaviruses have never been observed in non-avian reptiles, and only one member of the Circoviridae is known from a nonavian reptile (green sea turtle [61]).…”

“…20 species), with only a few cases known in other host species; one EVE found in the genomes of two species of birds (Hepadnaviridae [8,18,26]), mononegavirales-like sequences found in two species of teleostean fishes and in the lamprey [12,24], and a circovirus-and nanovirus-like sequence reported in the frog Xenopus tropicalis [27]. No nonretroviral EVEs have been comprehensively characterized in non-avian reptiles (but see [28]), which is probably owing to there being only one whole genome sequence available until very recently (the Carolina anole, Anolis carolinensis [29]). …”

Origin of an endogenous bornavirus-like nucleoprotein element in thirteen-lined ground squirrels

“…EBL elements homologous to N (EBLN) and G (EBLG) have been identified in the genomes of vertebrates, and those homologous to M (EBLM) and L (EBLL) in the genomes of vertebrates and invertebrates (Belyi et al, 2010;Horie et al, 2010Horie et al, , 2013Katzourakis and Gifford, 2010). It has been proposed that endogenous virus-like elements are involved in the protection against infection by homologous viruses (Arnaud et al, 2007;Aswad and Katzourakis, 2012).…”

“…In addition, since Borna disease is induced by immune responses to infected cells expressing Edited by Toshihiko Shiroishi * Corresponding author. E-mail: yossuzuk@nsc.nagoya-cu.ac.jp N (Planz and Stitz, 1999;Stitz et al, 2002), expression of proteins from EBLN elements may cause immunological tolerance to BDV infection (Horie et al, 2013). Therefore, even if anti-viral effects of EBLN are insufficient to prevent infection, infected organisms may survive, possibly serving as reservoirs (Belyi et al, 2010).…”