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Assembly of infectious enteroviruses depends on multiple, conserved genomic RNA-coat protein contacts.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Chandler-Bostock, Rebecca  ORCID logo  https://orcid.org/0000-0002-1225-4601
Dykeman, Eric C 
Meng, Bo 

Abstract

Picornaviruses are important viral pathogens, but despite extensive study, the assembly process of their infectious virions is still incompletely understood, preventing the development of anti-viral strategies targeting this essential part of the life cycle. We report the identification, via RNA SELEX and bioinformatics, of multiple RNA sites across the genome of a typical enterovirus, enterovirus-E (EV-E), that each have affinity for the cognate viral capsid protein (CP) capsomer. Many of these sites are evolutionarily conserved across known EV-E variants, suggesting they play essential functional roles. Cryo-electron microscopy was used to reconstruct the EV-E particle at ~2.2 Å resolution, revealing extensive density for the genomic RNA. Relaxing the imposed symmetry within the reconstructed particles reveals multiple RNA-CP contacts, a first for any picornavirus. Conservative mutagenesis of the individual RNA-contacting amino acid side chains in EV-E, many of which are conserved across the enterovirus family including poliovirus, is lethal but does not interfere with replication or translation. Anti-EV-E and anti-poliovirus aptamers share sequence similarities with sites distributed across the poliovirus genome. These data are consistent with the hypothesis that these RNA-CP contacts are RNA Packaging Signals (PSs) that play vital roles in assembly and suggest that the RNA PSs are evolutionarily conserved between pathogens within the family, augmenting the current protein-only assembly paradigm for this family of viruses.

Description

Keywords

Amino Acid Sequence, Capsid Proteins, Cryoelectron Microscopy, Enterovirus, RNA, Viral, Virus Assembly

Journal Title

PLoS Pathog

Conference Name

Journal ISSN

1553-7366
1553-7374

Volume Title

16

Publisher

Public Library of Science (PLoS)