High-resolution mass spectrometry of viral assemblies: Molecular composition and stability of dimorphic hepatitis B virus capsids

Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecul...

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Published inProceedings of the National Academy of Sciences - PNAS Vol. 105; no. 27; pp. 9216 - 9220
Main Authors Uetrecht, Charlotte, Versluis, Cees, Watts, Norman R, Roos, Wouter H, Wuite, Gijs J.L, Wingfield, Paul T, Steven, Alasdair C, Heck, Albert J.R
Format Journal Article
LanguageEnglish
Published United States National Academy of Sciences 08.07.2008
National Acad Sciences
Subjects
Average linear density
Biological Sciences
Capsid
Capsid - chemistry
Capsid - ultrastructure
Capsid proteins
Dimers
Electric potential
Hepatitis
Hepatitis B
Hepatitis B virus
Hepatitis B virus - chemistry
Hepatitis B virus - ultrastructure
Insects
Mass spectra
Mass Spectrometry
Mass spectroscopy
Microscopy, Atomic Force
Molecules
Monomers
Pathogens
Thermodynamics
Virus Assembly
Viruses
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Summary:Hepatitis B virus (HBV) is a major human pathogen. In addition to its importance in human health, there is growing interest in adapting HBV and other viruses for drug delivery and other nanotechnological applications. In both contexts, precise biophysical characterization of these large macromolecular particles is fundamental. HBV capsids are unusual in that they exhibit two distinct icosahedral geometries, nominally composed of 90 and 120 dimers with masses of [almost equal to]3 and [almost equal to]4 MDa, respectively. Here, a mass spectrometric approach was used to determine the masses of both capsids to within 0.1%. It follows that both lattices are complete, consisting of exactly 180 and 240 subunits. Nanoindentation experiments by atomic-force microscopy indicate that both capsids have similar stabilities. The data yielded a Young's modulus of [almost equal to]0.4 GPa. This experimental approach, anchored on very precise and accurate mass measurements, appears to hold considerable potential for elucidating the assembly of viruses and other macromolecular particles.
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Author contributions: A.J.R.H. designed research; C.U., C.V., N.R.W., and W.H.R. performed research; N.R.W., W.H.R., G.J.L.W., P.T.W., and A.C.S. contributed new reagents/analytic tools; C.U. and W.H.R. analyzed data; and C.U., N.R.W., W.H.R., G.J.L.W., P.T.W., A.C.S., and A.J.R.H. wrote the paper.
Edited by Fred W. McLafferty, Cornell University, Ithaca, NY, and approved April 25, 2008
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0800406105