Endogenous non-retroviral RNA virus elements in mammalian genomes

Abstract

Retroviruses are the only group of viruses known to have left a fossil record, in the form of endogenous proviruses, and some of 8% of the human genome is made up of these elements 1,2 . Although many other viruses, including non-retroviral RNA viruses, are known to generate DNA forms of their own genomes during replication3 , 4, none has been found as DNA in the germline of animals. Bornaviruses, a nonsegmented, negative-sense RNA virus, are unique among RNA viruses in that they establish persistent infection in the cell nucleus5 -7 . Here we show that elements homologous to the nucleoprotein (N) gene of Bornavirus exist in the genomes of several mammalian species, including humans, non-human primates, rodents and elephants. These sequences have been designated endogenous Bornalike N (EBLN) elements. Some of the primate EBLNs contain an intact open reading frame (ORF) and are expressed as mRNA. Phylogenetic analyses revealed that EBLNs appear to have been generated by different insertional events in each specific animal family. Furthermore, the EBLN of a ground squirrel was formed by a recent integration event, while those in primates must have been formed more than 40 million years ago. We also show that the N mRNA of a current mammalian Bornavirus, Borna disease virus (BDV), can form EBLN-like elements in the genomes of persistently infected cultured cells. Our results provide the first evidence for endogenization of non-retroviral virus-derived elements in mammalian genomes and give †To whom correspondence should be addressed. Dr. Keizo Tomonaga:

Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes

“…Furthermore, although it has been shown that endogenization could be catalysed by host retrotransposons [44], we did not detect any molecular signature (such as target-site duplications) indicating involvement of such mobile elements in snake EVEs endogenization.…”

“…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]).…”

“…In order to estimate the timing of the endogenization events producing the various EVEs that we detected, we followed an approach previously used in palaeovirology studies [18,26,44]. We used EVE-specific PCR primers to screen for the presence or absence of orthologous EVEs in viperid snakes with various degrees of relatedness to C. mitchellii.…”

Guest list or black list: heritable small RNAs as immunogenic memories

“…While the underlying mechanisms are unknown, it was discovered that the human genome contains bits and pieces of non-retrovirus RNA viruses [55,56]. A clue to the mechanism might be found in Drosophila, where in cells such integration was shown to be achieved by the reverse transcriptase activity of transposons, resulting in establishment of an anti-viral RNAi response [57].…”