Abstract
Virus assembly, a key stage in any viral life cycle, had long been considered to be primarily driven by protein-protein interactions and nonspecific interactions between genomic RNA and capsid protein. We review here a modelling paradigm for RNA virus assembly that illustrates the crucial roles of multiple dispersed, specific interactions between viral genomes and coat proteins in capsid assembly. The model reveals how multiple sequence-structure motifs in the genomic RNA, termed packaging signals, with a shared coat protein recognition motif enable viruses to overcome a viral assembly-equivalent of Levinthal's Paradox in protein folding. The fitness advantages conferred by this mechanism suggest that it should be widespread in viruses, opening up new perspectives on viral evolution and anti-viral therapy.
Highlights
The formation of a viral protein container encapsulating a virus’ genomic cargo is a prerequisite for the successful propagation of a viral infection
Instead of viewing viral genomes as passive passengers with at most non-specific electrostatic contributions to the assembly process, they demonstrate the consequences of the cooperative action of multiple, sequence-specific contacts between genomic RNA and coat protein (CP)
A mathematical model of packaging signal (PS)-mediated assembly In order to investigate how such multiple dispersed PS sites mediate capsid assembly, we developed a mathematical model that captures their collective impact on virus assembly efficiency (Figure 2) [37,38]
Summary
The formation of a viral protein container encapsulating a virus’ genomic cargo is a prerequisite for the successful propagation of a viral infection. Normal mode analysis has revealed the structural features of TR that are required for this allosteric effect [30,31], demonstrating that many other, multiple dispersed, stem–loops in the MS2 genome could trigger the same effect [32] This has resulted in the packaging signal (PS) hypothesis: Multiple dispersed secondary structure elements in the genomic RNA, with CP recognition features akin to those of the known high affinity PS, trigger conformational changes of the CP dimer to its asymmetric conformation. PSs can play a number of different roles in promoting capsid formation [35,36,45] These different scenarios all share the same basic mechanism of PS-mediated assembly, in which multiple dispersed sites in the (pre) genomic viral RNA with affinity for CP promote efficient formation of a viral capsid with the correct geometry.
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