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HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly

DOI: 10.1038/nmicrobiol.2017.98 DOI Help

Authors: Nikesh Patel (University of Leeds) , Simon J. White (University of Leeds) , Rebecca F. Thompson (University of Leeds) , Richard Bingham (University of York) , Eva U. Weiß (University of York) , Daniel P. Maskell (University of Leeds) , Adam Zlotnick (Indiana University) , Eric C. Dykeman (University of York) , Roman Tuma (University of Leeds) , Reidun Twarock (University of York) , Neil A. Ranson (University of Leeds) , Peter G. Stockley (University of Leeds)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Nature Microbiology , VOL 2

State: Published (Approved)
Published: June 2017
Diamond Proposal Number(s): 11164

Abstract: Formation of the hepatitis B virus nucleocapsid is an essential step in the viral lifecycle, but its assembly is not fully understood. We report the discovery of sequence-specific interactions between the viral pre-genome and the hepatitis B core protein that play roles in defining the nucleocapsid assembly pathway. Using RNA SELEX and bioinformatics, we identified multiple regions in the pre-genomic RNA with high affinity for core protein dimers. These RNAs form stem-loops with a conserved loop motif that trigger sequence-specific assembly of virus-like particles (VLPs) at much higher fidelity and yield than in the absence of RNA. The RNA oligos do not interact with preformed RNA-free VLPs, so their effects must occur during particle assembly. Asymmetric cryo-electron microscopy reconstruction of the T = 4 VLPs assembled in the presence of one of the RNAs reveals a unique internal feature connected to the main core protein shell via lobes of density. Biophysical assays suggest that this is a complex involving several RNA oligos interacting with the C-terminal arginine-rich domains of core protein. These core protein–RNA contacts may play one or more roles in regulating the organization of the pre-genome during nucleocapsid assembly, facilitating subsequent reverse transcription and acting as a nucleation complex for nucleocapsid assembly.

Journal Keywords: Cryoelectron microscopy; Hepatitis B virus; Virus structures

Subject Areas: Biology and Bio-materials

Diamond Offline Facilities: Electron Bio-Imaging Centre (eBIC)
Instruments: Krios I-Titan Krios I at Diamond

Added On: 24/11/2017 14:15

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