The picobirnavirus crystal structure provides functional insights into virion assembly and cell entry

Abstract

Double-stranded (ds) RNA virus particles are organized around a central icosahedral core capsid made of 120 identical subunits. This core capsid is unable to invade cells from outside, and animal dsRNA viruses have acquired surrounding capsid layers that are used to deliver a transcriptionally active core particle across the membrane during cell entry. In contrast, dsRNA viruses infecting primitive eukaryotes have only a simple core capsid, and as a consequence are transmitted only vertically. Here, we report the 3.4 Å X-ray structure of a picobirnavirus-an animal dsRNA virus associated with diarrhoea and gastroenteritis in humans. The structure shows a simple core capsid with a distinctive icosahedral arrangement, displaying 60 two-fold symmetric dimers of a coat protein (CP) with a new 3D-fold. We show that, as many nonenveloped animal viruses, CP undergoes an autoproteolytic cleavage, releasing a post-translationally modified peptide that remains associated with nucleic acid within the capsid. Our data also show that picobirnavirus particles are capable of disrupting biological membranes in vitro, indicating that its simple 120-subunits capsid has evolved animal cell invasion properties.

Animal Picobirnavirus

“…indicating that its simple 120-subunits capsid has evolved animal cell invasion properties [21]. Likewise, as per the published reports on porcine PBVs, in a few cases complete and almost-complete sequence identities were identified among clones derived from distinct animals, suggesting that PBV strains can be easily transmitted from one host to another [4].…”

“…These domains are the most exposed, and would be targeted by the adaptive immune system of vertebrates, as well as being responsible for interaction with an entry receptor that may vary from species to species. Serological studies of patients in which PBV has been detected are needed to understand the antigenicity of the virus [21].…”

“…Given the large number of microorganisms present in the intestinal flora of vertebrates, such speciescrossing events are likely to be more common than anticipated earlier. Similarly, as long as the resulting viruses remain apathogenic/asymptomatic for their new host, they are essentially unnoticed [21].…”

“…PBVs have been detected in faeces of humans and wide range of animal species with or without diarrhoea, worldwide. The virion is non-enveloped, small, spherical, 33-41 nm in diameter, with bisegmented dsRNA and consists of a simple core capsid with a distinctive icosahedral arrangement [21,63,68,82]. Based on the migration pattern of the bisegmented dsRNA, PBV appears either with large genome profile (2.3-2.6 kbp for the larger and 1.5-1.9 kbp for the smaller segment, respectively) [34,68] or small genome profile (1.75 and 1.55 kbp for segments 1 and 2, respectively) [6,26,27,34] in PAGE experiments.…”

Detection and Molecular Characterization of Porcine Picobirnavirus in Feces of Domestic Pigs from Kolkata, India

“…The ORF1 gene, in the segment 2, encodes for the viral RNAdependent RNA polymerase (RdRp) (534 amino acids). The virion structure consists of an outer capsid and a simple core inside with distinctive icosahedral arrangement [10].…”