Recombination of Retrotransposon and Exogenous RNA Virus Results in Nonretroviral cDNA Integration

Abstract

Retroviruses have the potential to acquire host cell-derived genetic material during reverse transcription and can integrate into the genomes of larger, more complex DNA viruses. In contrast, RNA viruses were believed not to integrate into the host's genome under any circumstances. We found that illegitimate recombination between an exogenous nonretroviral RNA virus, lymphocytic choriomeningitis virus, and the endogenous intracisternal A-type particle (IAP) retrotransposon occurred and led to reverse transcription of exogenous viral RNA. The resulting complementary DNA was integrated into the host's genome with an IAP element. Thus, RNA viruses should be closely scrutinized for any capacity to interact with endogenous retroviral elements before their approval for therapeutic use in humans.

Comprehensive analysis of endogenous bornavirus-like elements in eukaryote genomes

“…In addition, like LCMV, other retroelements may cause the integration of RNA viruses [57]. Although the mechanisms are still unclear, several other RNA viruses have been reported to be integrated into their host chromosomes [58][59][60][61][62].…”

“…Therefore, RNA viruses have the potential for integration of virus-derived segments. Thus, analysis of integration events is important for understanding the pathogenicity of RNA viruses and virus vectors [51,57,95]. …”

“…ERVs, retrotransposons and telomerase [70]. For example, an RNA segment of lymphocytic choriomeningitis virus (LCMV) is reverse-transcribed and integrated into its host cell chromosome by an intracisternal A-particle, an ERV element in the mouse genome [57].…”

“…However, integration of non-retroviral RNA viruses has been reported occasionally [57][58][59]. In addition, since 2004, germline integration of non-retroviral RNA viruses has been reported in insects and plants [60][61][62].…”

Living fossil or evolving virus?

“…Another important property of bornaviruses was uncovered recently by an international team of researchers (Horie et al, 2010): BDV was shown to integrate a DNA copy of its mRNA into the genetic mat erial of the host in persistently infected cells. Although other non-retroviral RNA viruses are known to produce DNA versions of their genomes during replication (Klenerman et al, 1997;Geuking et al, 2009), borna viruses are so far unique in having left endogenous fragments of themselves in the genomes of many mammalian species, including humans (Horie et al, 2010). At least four copies of these elements-homologous to the BDV nucleoprotein and thus named endogenous Borna-like nucleo protein (EBLN)-have been found in the human genome, and their orthologues in the genomes of other primates.…”