Dykeman, Eric Charles, Bingham, Richard John, Weiss, Eva Ursula et al. (1 more author) (2017) HBV RNA pre-genome encodes specific motifs that mediate interactions with the viral core protein that promote nucleocapsid assembly. Nature reviews. Microbiology. 17098. ISSN 1740-1534
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2017 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details. |
Dates: |
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Institution: | The University of York |
Academic Units: | The University of York > Faculty of Sciences (York) > Mathematics (York) The University of York > Faculty of Sciences (York) > Biology (York) |
Funding Information: | Funder Grant number THE ROYAL SOCIETY UNSPECIFIED |
Depositing User: | Pure (York) |
Date Deposited: | 07 Feb 2018 15:00 |
Last Modified: | 28 Jan 2025 00:07 |
Published Version: | https://doi.org/10.1038/nmicrobiol.2017.98 |
Status: | Published |
Refereed: | Yes |
Identification Number: | 10.1038/nmicrobiol.2017.98 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:127070 |
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