Vertebrate-tropism of a Cressdnavirus Lineage Implicated by Poxvirus Gene Capture

Among cressdnaviruses, only the family is recognized to infect vertebrates, while many others have unknown hosts. Detection of virus-to-host horizontal gene transfer is useful for solving such virus-host relationships. Here, we extend this utility to an unusual case of virus-to-virus horizontal transfer, showing multiple ancient captures of cressdnavirus genes by avipoxviruses-large dsDNA pathogens of birds and other saurians. As gene transfers must have occurred during virus coinfections, saurian hosts were implied for the cressdnavirus donor lineage. Surprisingly, phylogenetic analysis revealed that donors were not members of the vertebrate-infecting , instead belonging to a previously unclassified family that we name . While draupnirviruses still circulate today, we show that those in the genus infected saurian vertebrates at least 114 Mya, leaving endogenous viral elements inside snake, lizard, and turtle genomes throughout the Cretaceous Period. Endogenous krikovirus elements in some insect genomes and frequent detection in mosquitoes imply that spillover to vertebrates was arthropod mediated, while ancestral draupnirviruses likely infected protists before their emergence in animals. A modern krikovirus sampled from an avipoxvirus-induced lesion shows that their interaction with poxviruses is ongoing. Captured genes in poxvirus genomes often have inactivated catalytic motifs, yet near-total presence across the genus, and evidence of both expression and purifying selection on them suggests currently unknown functions.