RNA topology remolds electrostatic stabilization of viruses

Erdemci-Tandogan, Gonca; Wagner, Jef; Schoot, Paul van der; Podgornik, Rudolf; Zandi, Roya

doi:10.1103/physreve.89.032707

Cited by 56 publications

(83 citation statements)

References 40 publications

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“…Non-specific electrostatic interactions have emerged as the driving force for virus assembly through both the experimental as well as the theoretical studies [9,14,24,27,28]. In our two simple models we generalized the implementation of electrostatic interactions by coupling it to RNA topology.…”

Section: Discussion and Summarymentioning

confidence: 99%

“…The overcharging phenomenon has been discussed in many theoretical papers with different conclusions dependening mostly on the details of the model under consideration [26][27][28][29][30][31][32][33]. What one would hope for is that the important characteristics of the RNA genome packaging would robustly depend on some well defined characteristics of the genome, a hypothesis recently proposed in our work [24], where we showed that the secondary structure of RNA, as quantified by its branchiness, coupled to electrostatic interactions enhances the genome encapsidation capacity and could robustly explain the overcharging actually observed in virions.…”

Section: Introductionmentioning

confidence: 95%

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Effects of RNA branching on the electrostatic stabilization of viruses

et al. 2016

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Many single-stranded (ss) RNA viruses self assemble from capsid protein subunits and the nucleic acid to form an infectious virion. It is believed that the electrostatic interactions between the negatively charged RNA and the positively charged viral capsid proteins drive the encapsidation, although there is growing evidence that the sequence of the viral RNA also plays a role in packaging. In particular the sequence will determine the possible secondary structures that the ssRNA will take in solution. In this work, we use a mean field theory to investigate how the secondary structure of the RNA combined with electrostatic interactions affects the efficiency of assembly and stability of the assembled virions. We show that the secondary structure of RNA may result in negative osmotic pressures while a linear polymer causes positive osmotic pressures for the same conditions. This may suggest that the branched structure makes the RNA more effectively packaged and the virion more stable.

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Section: Discussion and Summarymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

Effects of RNA branching on the electrostatic stabilization of viruses

et al. 2016

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“…Specifically, the observation that the interiors of most RNA viruses are (negatively) overcharged (2), meaning that the negative charge brought by the nucleic acid is greater than the positive charge brought by the basic residues lining the interior of the capsid, has been examined in detail (9)(10)(11)(12). While recent coarse-grained molecular dynamics simulations (11,(13)(14)(15)(16)(17) have begun to elucidate the role of electrostatics during assembly, experimental data remain scarce due to the difficulty of resolving the inherently short-lived assembly intermediates.…”

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confidence: 99%

Role of Electrostatics in the Assembly Pathway of a Single-Stranded RNA Virus

Garmann

Comas-García

Koay

et al. 2014

J Virol

105

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We have recently discovered (R. D. Cadena-Nava et al., J. Virol. 86:3318 -3326, 2012, doi:10.1128/JVI.06566-11) that the in vitro packaging of RNA by the capsid protein (CP) of cowpea chlorotic mottle virus is optimal when there is a significant excess of CP, specifically that complete packaging of all of the RNA in solution requires sufficient CP to provide charge matching of the N-terminal positively charged arginine-rich motifs (ARMS) of the CPs with the negatively charged phosphate backbone of the RNA. We show here that packaging results from the initial formation of a charge-matched protocapsid consisting of RNA decorated by a disordered arrangement of CPs. This protocapsid reorganizes into the final, icosahedrally symmetric nucleocapsid by displacing the excess CPs from the RNA to the exterior surface of the emerging capsid through electrostatic attraction between the ARMs of the excess CP and the negative charge density of the capsid exterior. As a test of this scenario, we prepare CP mutants with extra and missing (relative to the wild type) cationic residues and show that a correspondingly smaller and larger excess, respectively, of CP is needed for complete packaging of RNA. IMPORTANCECowpea chlorotic mottle virus (CCMV) has long been studied as a model system for the assembly of single-stranded RNA viruses. While much is known about the electrostatic interactions within the CCMV virion, relatively little is known about these interactions during assembly, i.e., within intermediate states preceding the final nucleocapsid structure. Theoretical models and coarse-grained molecular dynamics simulations suggest that viruses like CCMV assemble by the bulk adsorption of CPs onto the RNA driven by electrostatic attraction, followed by structural reorganization into the final capsid. Such a mechanism facilitates assembly by condensing the RNA for packaging while simultaneously concentrating the local density of CP for capsid nucleation. We provide experimental evidence of such a mechanism by demonstrating that efficient assembly is initiated by the formation of a disordered protocapsid complex whose stoichiometry is governed by electrostatics (charge matching of the anionic RNA and the cationic N termini of the CP).

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“…We note here that while for simplicity we employed linear chains for all the calculations in this paper, we also studied the impact of branching (following the techniques used in Ref. 32 ) on the final results. Including the secondary structures of RNA makes the chain more compact and lower the free energy values for both cylindrical and conical shells, but do not change the conclusion of the paper.…”

Section: Modelmentioning

confidence: 99%

“…[23][24][25][26][27][28][29][30][31][32][33][34][35] Since the focus of this paper is on HIV particles, we employ Edwards-de GennesLifshitz theory to calculate the free energy of a linear polymer confined in a cylindrical and conical shell. [36][37][38] In the ground-state approximation of long chains, it reads…”

Section: Modelmentioning

confidence: 99%

Role of Genome in the Formation of Conical Retroviral Shells

et al. 2016

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Human immunodeficiency virus (HIV) capsid proteins spontaneously assemble around the genome into a protective protein shell called the capsid, which can take on a variety of shapes broadly classified as conical, cylindrical and irregular. The majority of capsids seen in in vivo studies are conical in shape, while in vitro experiments have shown a preference for cylindrical capsids. The factors involved in the selection of the unique shape of HIV capsids are not well understood, and in particular the impact of RNA on the formation of the capsid is not known. In this work, we study the role of the genome and its interaction with the capsid protein by modeling the genomic RNA through a mean-field theory. Our results show that the confinement free energy for a homopolymeric model genome confined in a conical capsid is

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RNA topology remolds electrostatic stabilization of viruses

Cited by 56 publications

References 40 publications

Effects of RNA branching on the electrostatic stabilization of viruses

Effects of RNA branching on the electrostatic stabilization of viruses

Role of Electrostatics in the Assembly Pathway of a Single-Stranded RNA Virus

Role of Genome in the Formation of Conical Retroviral Shells

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