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Publication Abstract from PubMed

Despite their diversity, most double-stranded (ds)RNA viruses share a specialized T=1 capsid built from dimers of a single protein that provides a platform for genome transcription and replication. This ubiquitous capsid remains structurally undisturbed throughout the viral cycle, isolating the genome to avoid triggering host defense mechanisms. Human picobirnavirus (hPBV) is a dsRNA virus frequently associated with gastroenteritis, although its pathogenicity is yet undefined. Here we report the cryo-EM structure of hPBV at 2.6 A resolution. The capsid protein (CP) is arranged in a single-shelled, approximately 380-A-diameter T=1 capsid with a rough outer surface similar to dsRNA mycoviruses. The hPBV capsid is built of 60 quasi-symmetric CP dimers (A and B) stabilized by domain swapping, and only the CP-A N-terminal basic region interacts with the packaged nucleic acids. hPBV CP has an alpha-helical domain with a fold similar to fungal partitivirus CP, with many domain insertions in its C-terminal half. In contrast to dsRNA mycoviruses, hPBV have an extracellular life cycle phase like complex reoviruses, which indicates that its own CP probably participates in cell entry. Using an in vitro reversible assembly/disassembly system of hPBV, we isolated tetramers as possible assembly intermediates. We used atomic force microscopy to characterize the biophysical properties of hPBV capsids with different cargos (host nucleic acids or proteins), and found that the CP N-terminal segment is involved not only in nucleic acid interaction/packaging, but also modulates the mechanical behavior of the capsid in conjunction with the cargo.IMPORTANCE Despite intensive study, human virus sampling is still sparse, especially for those that cause mild or asymptomatic disease. Human picobirnavirus (hPBV) is a double-stranded RNA virus, broadly extended in the human population, but its pathogenicity is uncertain. Here we report the hPBV structure derived from cryo-electron microscopy (cryo-EM) and reconstruction methods using three capsid protein variants (of different lengths and N-terminal amino acid compositions) that assemble as virus-like particles with distinct properties. The hPBV near-atomic structure reveals a quasi-symmetric dimer as the structural subunit, and tetramers as possible assembly intermediates that co-assemble with nucleic acids. Our structural studies and atomic force microscopy analyses indicate that hPBV capsids are potentially excellent nanocages for gene therapy and targeted drug delivery in humans.

Cryo-EM structure, assembly, and mechanics show morphogenesis and evolution of human picobirnavirus.,Ortega-Esteban A, Mata CP, Rodriguez-Espinosa MJ, Luque D, Irigoyen N, Rodriguez JM, de Pablo PJ, Caston JR J Virol. 2020 Sep 16. pii: JVI.01542-20. doi: 10.1128/JVI.01542-20. PMID:32938763^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.