100-My history of bornavirus infections hidden in vertebrate genomes

Abstract

Although viruses have threatened our ancestors for millions of years, prehistoric epidemics of viruses are largely unknown. Endogenous bornavirus-like elements (EBLs) are ancient bornavirus sequences derived from the viral messenger RNAs that were reverse transcribed and inserted into animal genomes, most likely by retrotransposons. These elements can be used as molecular fossil records to trace past bornaviral infections. In this study, we systematically identified EBLs in vertebrate genomes and revealed the history of bornavirus infections over nearly 100 My. We confirmed that ancient bornaviral infections have occurred in diverse vertebrate lineages, especially in primate ancestors. Phylogenetic analyses indicated that primate ancestors were infected with various bornaviral lineages during evolution. EBLs in primate genomes formed clades according to their integration ages, suggesting that bornavirus lineages infected with primate ancestors had changed chronologically. However, some bornaviral lineages may have coexisted with primate ancestors and underwent repeated endogenizations for tens of millions of years. Moreover, a bornaviral lineage that coexisted with primate ancestors also endogenized in the genomes of some ancestral bats. The habitats of these bat ancestors have been reported to overlap with the migration route of primate ancestors. These results suggest that long-term virus–host coexistence expanded the geographic distributions of the bornaviral lineage along with primate migration and may have spread their infections to these bat ancestors. Our findings provide insight into the history of bornavirus infections over geological timescales that cannot be deduced from research using extant viruses alone, thus broadening our perspective on virus–host coevolution.

Discovery of Flaviviridae-derived endogenous viral elements in shrew genomes provide novel insights into Pestivirus ancient history

“…Similarly, the discovery of abundant bornavirus-like EVEs across vertebrates reveals that ancient bornaviral infections occurred over a timeframe of about 100 million years before present (Kawasaki et al, 2021). These studies can also provide genetic fossil calibration points for further gauging ancient viral timescales using phylogenetics (Feschotte and Gilbert, 2012).…”

“…For example, EVEs derived from adeno-associated viruses appear to be orthologous in African and Asian elephants, indicating an integration event more than 6 million years ago (Kobayashi et al, 2019). Similarly, the discovery of abundant bornavirus-like EVEs across vertebrates reveals that ancient bornaviral infections occurred over a timeframe of about 100 million years before present (Kawasaki et al, 2021). These studies can also provide genetic fossil calibration points for further gauging ancient viral timescales using phylogenetics (Feschotte and Gilbert, 2012).…”

Mapping the evolution of bornaviruses across geological timescales

“…Increasingly, the challenge is not finding EVEs, but scaling analytical approaches to tackle the exponentially increasing volume of EVE sequence data (3,4). In PNAS, Kawasaki et al (5) utilize sophisticated computational approaches to implement a broad-scale analysis of the viral "fossil record," focusing on a group of viruses called "bornaviruses. "…”

Viral fossils in marsupial genomes: secret cellular guardians

“…If these integrations occur in germline cells, they are inherited by progeny and can spread through a population. These viral remnants, also known as endogenous viral elements (EVEs), are in every known vertebrate and invertebrate and provide an extensive history of viral evolution 2,3 .…”

“…Of these proteins, two were consistently represented in RNA sequencing datathe nucleocapsid, or shell, and the polymerase or replication gene. Bornavirus and filovirus nucleoprotein EVEs are commonly found throughout mammals; however, the bornavirus polymerase is much rarerbats are the only other mammalian group with this type of EVE 3 . In contrast to trends in other mammals, marsupials had high amounts of RNA derived from these bornavirus polymerase EVEs, and the small RNA was predominantly from these.…”