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.

尽管病毒已经威胁我们的祖先数百万年，但史前病毒的流行在很大程度上是未知的。内源性博纳病毒样元件 (EBL) 是源自病毒信使 RNA 的古老博纳病毒序列，这些序列被逆转录并插入动物基因组中，最有可能是通过逆转录转座子。这些元素可以用作分子化石记录来追踪过去的出生病毒感染。在这项研究中，我们系统地鉴定了脊椎动物基因组中的 EBL，并揭示了近 100 My 的博纳病毒感染历史。我们证实古代出生病毒感染发生在不同的脊椎动物谱系中，尤其是在灵长类动物的祖先中。系统发育分析表明，灵长类祖先在进化过程中感染了各种出生病毒谱系。灵长类动物基因组中的 EBL 根据其整合年龄形成进化枝，这表明感染了灵长类动物祖先的博纳病毒谱系已按时间顺序发生变化。然而，一些出生病毒谱系可能与灵长类祖先共存，并经历了数千万年的反复内源化。此外，与灵长类祖先共存的出生病毒谱系也在一些祖先蝙蝠的基因组中内源化。据报道，这些蝙蝠祖先的栖息地与灵长类动物祖先的迁徙路线重叠。这些结果表明，长期的病毒-宿主共存扩大了出生病毒谱系的地理分布以及灵长类动物的迁徙，并可能将它们的感染传播给了这些蝙蝠祖先。