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Surface stresses in complex viral capsids and non-quasi-equivalent viral architectures.

ABSTRACT: Many larger and more complex viruses deviate from the capsid layouts predicted in the seminal Caspar-Klug theory of icosahedral viruses. Instead of being built from one type of capsid protein (CP), they code for multiple distinct structural proteins that either break the local symmetry of the CP building blocks (capsomers) in specific positions or exhibit auxiliary proteins that stabilize the capsid shell. We investigate here the hypothesis that this occurs as a response to mechanical stress. For this, we construct a coarse-grained model of a viral capsid, derived from the experimentally determined atomistic positions of the CPs, that represents the basic features of protein organization in the viral capsid as described in Caspar-Klug theory. We focus here on viruses in the PRD1-adenovirus lineage. For T = 28 viruses in this lineage, which have capsids formed from two distinct structural proteins, we show that the tangential shear stress in the viral capsid concentrates at the sites of local symmetry breaking. In the T = 21, 25 and 27 capsids, we show that stabilizing proteins decrease the tangential stress. These results suggest that mechanical properties can act as selective pressures on the evolution of capsid components, offsetting the coding cost imposed by the need for such additional protein components.

SUBMITTER: Indelicato G

PROVIDER: S-EPMC7482553 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Surface stresses in complex viral capsids and non-quasi-equivalent viral architectures.

Indelicato Giuliana G Cermelli Paolo P Twarock Reidun R

Journal of the Royal Society, Interface 20200805 169

Many larger and more complex viruses deviate from the capsid layouts predicted in the seminal Caspar-Klug theory of icosahedral viruses. Instead of being built from one type of capsid protein (CP), they code for multiple distinct structural proteins that either break the local symmetry of the CP building blocks (capsomers) in specific positions or exhibit auxiliary proteins that stabilize the capsid shell. We investigate here the hypothesis that this occurs as a response to mechanical stress. Fo ...[more]

PMID: 32752992

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Project description:Beta-propiolactone (BPL) is an inactivating agent that is widely used in the vaccine industry. However, its effects on vaccine protein antigens and its mechanisms of action remain poorly understood. Here we present cryo-electron microscopy (cryo-EM) structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids at resolutions of 3.9 Å and 6.5 Å, respectively. Notably, both particles were found to adopt an expanded conformation resembling the 135S-like uncoating intermediate, with characteristic features including an opened 2-fold channel, the externalization of the N terminus of VP1 capsid protein, and the absence of pocket factor. However, major neutralizing epitopes are very well preserved on these particles. Further biochemical analyses revealed that BPL treatment impairs the abilities of CVA16 particles to bind to the attachment receptor heparan sulfate and to a conformation-dependent monoclonal antibody in a BPL dose-dependent manner, indicating that BPL is able to modify surface-exposed amino acid residues. Taken together, our results demonstrate that BPL treatment may induce alteration of the overall structure and surface properties of a nonenveloped viral capsid, thus revealing a novel mode of action of BPL.IMPORTANCE Beta-propiolactone (BPL) is commonly used as an inactivating reagent to produce viral vaccines. It is recognized that BPL inactivates viral infectivity through modification of viral nucleic acids. However, its effect on viral proteins remains largely unknown. Here, we present high-resolution cryo-EM structures of BPL-treated coxsackievirus A16 (CVA16) mature virions and procapsids, which reveals an expanded overall conformation and characteristic features that are typical for the 135S-like uncoating intermediate. We further show that the BPL concentration affects the binding of inactivated CVA16 particles to their receptor/antibody. Thus, BPL treatment can alter the overall structure and surface properties of viral capsids, which may lead to antigenic and immunogenic variations. Our findings provide important information for future development of BPL-inactivated vaccines.

Dataset Information

Surface stresses in complex viral capsids and non-quasi-equivalent viral architectures.

Publications

Surface stresses in complex viral capsids and non-quasi-equivalent viral architectures.

Similar Datasets

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