The effect of RNA stiffness on the self-assembly of virus particles

Abstract

Under many in vitro conditions, some small viruses spontaneously encapsidate a single stranded (ss) RNA into a protein shell called the capsid. While viral RNAs are found to be compact and highly branched because of long distance base-pairing between nucleotides, recent experiments reveal that in a head-to-head competition between a ssRNA with no secondary or higher order structure and a viral RNA, the capsid proteins preferentially encapsulate the linear polymer! In this paper, we study the impact of genome stiffness on the encapsidation free energy of the complex of RNA and capsid proteins. We show that an increase in effective chain stiffness because of base-pairing could be the reason why under certain conditions linear chains have an advantage over branched chains when it comes to encapsidation efficiency. While branching makes the genome more compact, RNA base-pairing increases the effective Kuhn length of the RNA molecule, which could result in an increase of the free energy of RNA confinement, that is, the work required to encapsidate RNA, and thus less efficient packaging.

Nonequilibrium self-assembly dynamics of icosahedral viral capsids packaging genome or polyelectrolyte

“…The latter, which is very flexible, might then collapse through a coil–globule transition that could allow the bound subunits to contact each other and to build up a closed shell, despite the energy barrier related to their electrostatic repulsion and to the conformational change required to arrange onto an icosahedral lattice. A recent theoretical study demonstrated that flexible, linear chains require less free energy than stiff, branched ones to be confined in a capsid 47 , which is in qualitative agreement with our results. Like virions, PSS-filled capsids are stable against dilution, which indicates that, at the end of assembly, the subunits making up the capsid are no longer able to exchange with the bulk solution.…”

A modelling paradigm for RNA virus assembly

“…An important aspect of virus assembly in the presence of genomic RNA is the need for genome compaction [ 10 ], and several groups have made important contributions to the modelling of this aspect of virus assembly [ 11 • , 12 , 13 • , 14 • ]. The impact of non-specific electrostatic interactions between genomic RNAs and CP [ 15 , 16 , 17 , 18 , 19 •• ] and of the stiffness of the RNA molecule on the assembly process [ 20 • ] have been analysed. It has also been shown that the secondary structure of the RNA molecules play an essential role in determining capsid morphology in the self-assembly of Cowpea Chlorotic Mottle Virus (CCMV)-like particles [ 21 ].…”

Virus-Like Particles Produced Using the Brome Mosaic Virus Recombinant Capsid Protein Expressed in a Bacterial System

“…The authors also explain this effect by the hydrophobic properties of PSS, which is poorly soluble in water and exists in a collapsed form [ 24 ]. Moreover, they noted that linear, flexible PSS chains require less free energy to be encapsulated than particles with stiff conformations, such as RNA [ 24 , 30 ].…”