Are picobirnaviruses actually RNA bacteriophage rather than eukaryotic viruses?
The Wang lab has a longstanding interest in defining the role of the virome in health and disease. The first step entails metagenomic sequencing to identify known and novel viruses present in a given sample set. In the course of these studies, the highest priority for follow up studies is often placed on novel viruses that are clearly related to established human pathogens (i.e “popular viruses”) with less emphasis on those that are not linked to pathogenic viral families (i.e “unpopular viruses”). Here, we focused on characterizing one of the most commonly detected “unpopular viruses”, the family Picobirnaviridae. This study arose when Sidd, the first author of the study, identified 38 novel picobirnavirus sequences from stool samples from a single cohort of macaques. Although there are some claims in the literature that picobirnaviruses are diarrhea agents, this is based solely on anecdotal case reports.
After extensive discussions in the lab about the possible links between picobirnaviruses and disease, on a mid-July Friday afternoon, Dave off-handedly suggested to Sidd that picobirnaviruses might infect bacteria. Having recently completed a project on the diversity of RNA bacteriophages, Sidd was intrigued by this hypothesis, as there are only two known families of RNA bacteriophages. He thought about what genomic information could be leveraged to discern whether picobirnaviruses infect bacteria and remembered that bacterial RNA viruses often encode a conserved nucleotide sequence upstream of their genes to initiated translation, called the ribosomal binding site (RBS) or Shine-Dalgarno sequence. As eukaryotes do not use this sequence to initiate translation, he surmised that if picobirnaviruses conserved the RBS sequence, it might suggest that they infect bacteria.
So, he downloaded the genome sequences of Human Picobirnavirus and found RBS sequences in front of its 3 genes. He then checked all the other deposited picobirnavirus genomes within the database, as well as the 38 novel picobirnavirus genomes; shockingly, they all conserved RBS sequences. Sidd computationally analyzed genes from all other DNA and RNA viruses that infect bacteria or eukaryotes and confirmed that only bacterial viruses consistently conserve the RBS sequence.
This study suggests that picobirnaviruses might be the 3rd known family of RNA bacteriophages. If true, this necessitates a paradigm shift in how we think about the role of these viruses in human health. Finally, it suggests that RNA bacteriophages frequently inhabit the human microbiome and raises the possibility that more RNA bacteriophages are yet to be discovered.
Picobirnavirus ORFs are all preceded by at least a 4 nt prokaryotic ribosome binding site sequence, suggesting they may infect prokaryotes
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About the research
Extensive conservation of prokaryotic ribosomal binding sites in known and novel picobirnaviruses
Virology, Volume 516, March 2018, Pages 108-114
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