Picobirnaviruses encode proteins that are functional bacterial lysins.

Picobirnaviruses (PBVs) are double-stranded RNA viruses frequently detected in human and animal enteric viromes. Associations of PBVs with enteric graft-versus-host disease and type I diabetes during pregnancy have been established. Since their discovery in 1988, PBVs have been generally assumed to be animal-infecting viruses despite the lack of culture system, animal model, or detection in animal cells or tissues. Recent studies have proposed that bacteria or fungi could be the hosts of PBVs based on genomic analysis. Here, we functionally demonstrate that multiple PBVs of different genome organizations encode bacterial lysins that lyse . Such genes are typically encoded only by bacteriophages supporting the model that PBVs infect bacterial hosts. Recognition of PBVs as RNA phages in the human gut would completely shift models of how PBVs could impact human health. In addition, expanding the RNA phage world beyond the two recognized clades to three clades has implications for our understanding of the evolution of RNA viruses.