Packaging of a Polymer by a Viral Capsid: The Interplay between Polymer Length and Capsid Size

Hu, Yufang; Zandi, Roya; Anavitarte, Adriana; Knobler, Charles M.; Gelbart, William M.

doi:10.1529/biophysj.107.117473

Cited by 200 publications

(274 citation statements)

References 47 publications

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“…9 These have been compared to socalled "monster" structures that were found in in vitro studies of the assembly of turnip crinkle virus and capsid protein around the viral RNA. 10 12 correspond to Caspar-Klug structures with T ) 1, 3, 4, and 7; a so-called pseudo-Caspar-Klug structure with T ) 2 is also known. 13 The relative diameters of the capsids are related to their T numbers by the expression because the capsid surface area is proportional to T (and D 2 ).…”

Section: Resultsmentioning

confidence: 99%

Phase Diagram of Self-assembled Viral Capsid Protein Polymorphs

et al. 2009

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We present an experimental study of the self-assembly of capsid proteins of the cowpea chlorotic mosaic virus (CCMV), in the absence of the viral genome, as a function of pH and ionic strength. In accord with previous measurements, a wide range of polymorphs can be identified by electron microscopy, among them single and multiwalled shells and tubes. The images are analyzed with respect to size and shape of aggregates, and evidence is given that equilibrium has been achieved, allowing a phase diagram to be constructed. Some previously unreported structures are also described. The range and stability of the polymorphs can be understood in terms of electrostatic interactions and the way they affect the spontaneous curvature of protein networks and the relative stabilities of pentamers and hexamers.

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Section: Resultsmentioning

confidence: 99%

Phase Diagram of Self-assembled Viral Capsid Protein Polymorphs

et al. 2009

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“…49,50 Examples include Flock house virus, which has a charge ratio of 1.4, and Brome mosaic virus, which ranges from 1.56 to 1.79 depending on the RNA fragment being encapsidated. Consistent with the electrostatic interaction driving assembly, previous work also showed that deletions of the basic residues in the CP results in reduced packaging of viral RNA.…”

Section: ■ Discussionmentioning

confidence: 99%

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

Fan

Tsvetkova²,

Khuong³

et al. 2012

Mol. Pharmaceutics

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Viral nanoparticles used for biomedical applications must be able to discriminate between tumor or virus-infected host cells and healthy host cells. In addition, viral nanoparticles must have the flexibility to incorporate a wide range of cargo, from inorganic metals to mRNAs to small molecules. Alphaviruses are a family of enveloped viruses for which some species are intrinsically capable of systemic tumor targeting. Alphavirus virus-like particles, or viral nanoparticles, can be generated from in vitro self-assembled core-like particles using nonviral nucleic acid. In this work, we expand on the types of cargo that can be incorporated into alphavirus core-like particles and the molecular requirements for packaging this cargo. We demonstrate that different core-like particle templates can be further enveloped to form viral nanoparticles that are capable of cell entry. We propose that alphaviruses can be selectively modified to create viral nanoparticles for biomedical applications and basic research.

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“…The thermodynamic framework developed in this study should be useful for interpreting results from experimental studies of in vitro assembly of viruses and virus-like particles (22)(23)(24)(25)(26), as well as for the design of viral vectors for gene therapy, where, in addition to minimizing toxicity, a major goal is to successfully deliver the appropriate amount of therapeutic gene (27). More generally, because the presence of charged macromolecules in cells is ubiquitous, we expect the associated Donnan effects, much like the well known crowding effects (28), to significantly influence a wide range of biomacromolecular behaviors and cellular processes.…”

Section: Discussionmentioning

confidence: 99%

Thermodynamic basis for the genome to capsid charge relationship in viral encapsidation

Ting

Wang

2011

Proc. Natl. Acad. Sci. U.S.A.

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We establish an appropriate thermodynamic framework for determining the optimal genome length in electrostatically driven viral encapsidation. Importantly, our analysis includes the electrostatic potential due to the Donnan equilibrium, which arises from the semipermeable nature of the viral capsid, i.e., permeable to small mobile ions but impermeable to charged macromolecules. Because most macromolecules in the cellular milieu are negatively charged, the Donnan potential provides an additional driving force for genome encapsidation. In contrast to previous theoretical studies, we find that the optimal genome length is the result of combined effects from the electrostatic interactions of all charged species, the excluded volume and, to a very significant degree, the Donnan potential. In particular, the Donnan potential is essential for obtaining negatively overcharged viruses. The prevalence of overcharged viruses in nature may suggest an evolutionary preference for viruses to increase the amount of genome packaged by utilizing the Donnan potential (through increases in the capsid radius), rather than high charges on the capsid, so that structural stability of the capsid is maintained.polyelectrolyte | viral assembly T he most prevalent viruses in nature are single-stranded RNA viruses with the genetic material enclosed in icosahedral-shaped capsids made up of 60 T protein units, where the T-number is a small integer index. The protein units (capsomers) often contain highly basic peptide arms that extend into the capsid interior and, under physiological conditions, are positively charged. Electrostatic attraction provides the driving force for encapsidating the negatively charged RNA, which, in turn, helps overcome the electrostatic repulsion among the capsomers during the capsid assembly.In a series of classic experiments, Bancroft and coworkers (1, 2) demonstrated that certain viruses can encapsidate nonnative RNA and even generic polyanions. Dominance of the electrostatics as the driving force for viral assembly has led to the expectation of a simple relationship between the total capsid charge Q P and the genome charge Q R , as every nucleotide carries one unit of negative charge. Belyi and Muthukumar (3) compiled data for 19 wild type viruses from several viral families and found an apparent "universal" charge ratio of Q R ∕Q P ≈ 1.6, which they explained by combining the ground-state dominance approximation for polyelectrolyte binding to an oppositely charged polymer brush with the Manning condensation theory (4). The former predicts a 1∶1 charge ratio and the latter is used as a qualitative argument for the actual charge on the RNA being less than the nominal charge. Hu, et al. (5), however, assumed that the RNA winds around individual peptide arms and found that the viruses are most stable when the total contour length of the RNA is close to the total length of the peptide arms; this roughly gives a charge ratio of 2. In other works that ignore the peptide arms completely, there is additional disagreemen...

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Packaging of a Polymer by a Viral Capsid: The Interplay between Polymer Length and Capsid Size

Cited by 200 publications

References 47 publications

Phase Diagram of Self-assembled Viral Capsid Protein Polymorphs

Phase Diagram of Self-assembled Viral Capsid Protein Polymorphs

The Packaging of Different Cargo into Enveloped Viral Nanoparticles

Thermodynamic basis for the genome to capsid charge relationship in viral encapsidation

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