Picobirnavirus reclassified as bacteriophage, not human pathogen

A study published in Nature Microbiology on October 29, 2026, by researchers at Washington University School of Medicine in St. Louis revealed that picobirnaviruses infect gut bacteria rather than human cells. First discovered in 1988 and long assumed to be a human pathogen causing diarrhea, the virus represents only the third known clade of RNA bacteriophages. Using germ-free mouse models and anaerobic cell sorting, researchers confirmed propagation inside a newly identified bacterium, Candidatus Anaerotignum faecalis.

Reclassification as RNA bacteriophages

• ▪Picobirnaviruses represent only the third known clade of RNA viruses that infect bacteria, joining leviviruses and cystoviruses discovered in 1961 and 1973.
• ▪A study established that Picobirnaviridae is an RNA bacteriophage family that infects bacteria rather than human cells

In vivo mouse model experiments

• ▪Researchers led by Tianyu Gan and David Wang established an in vivo model by gavaging germ-free mice with human stool samples to propagate picobirnaviruses.
• ▪Treatment of gavaged mice with the antibiotic neomycin eliminated PBV-19022, indicating that the virus depends on an antibiotic-sensitive bacterial host.
• ▪Two human stool-derived picobirnaviruses, named PBV-18941 and PBV-19022, increased RNA quantity over 100-fold and persisted through 23 days in germ-free mice.

In vitro culture and cellular localization

• ▪Treatment with neomycin, vancomycin, and metronidazole eliminated PBV-18941 in anaerobic culture, whereas ampicillin, kanamycin, chloramphenicol, and tetracycline did not inhibit viral growth.
• ▪RNA fluorescence in situ hybridization demonstrated that PBV-18941 RNA segment 1 and segment 2 colocalize inside bacterial cells, confirming picobirnavirus is a bacteriophage.
• ▪Researchers propagated PBV-18941 in vitro for 20 passages in an anaerobic microbial community culture derived from mouse stool pellets.

Identification of the bacterial host

• ▪Candidatus Anaerotignum faecalis shares 96% identity in the 16S rRNA V4 region with its closest relative, Anaerotignum aminivorans.
• ▪Using cell sorting and 16S rRNA sequencing, researchers identified a newly discovered obligate anaerobic rod bacterium, Candidatus Anaerotignum faecalis, as the host for PBV-18941.

Implications for human health

• ▪David Wang stated that picobirnaviruses could impact human health indirectly by destroying beneficial gut bacteria or serving as biomarkers for gut ecosystem distress.
• ▪Picobirnaviruses have been associated with enteric graft-versus-host disease, irritable bowel syndrome, type 1 diabetes, and acute diarrhea in patients.

Origins of the host investigation

• ▪First discovered in 1988 from human stool samples, picobirnaviruses were assumed for decades to directly infect human cells and cause gastrointestinal diseases.
• ▪Researchers in David Wang's laboratory unexpectedly detected picobirnavirus genetic material while studying Caenorhabditis elegans roundworms, prompting investigation into bacterial hosts.