title: Vertex-Specific Proteins pUL17 and pUL25 Mechanically Reinforce Herpes Simplex Virus Capsids.
abstract: Using atomic force microscopy imaging and nanoindentation measurements, we investigated the effect of the minor capsid proteins pUL17 and pUL25 on the structural stability of icosahedral herpes simplex virus capsids. pUL17 and pUL25, which form the capsid vertex-specific component (CVSC), particularly contributed to capsid resilience along the 5-fold and 2-fold but not along the 3-fold icosahedral axes. Our detailed analyses, including quantitative mass spectrometry of the protein composition of the capsids, revealed that both pUL17 and pUL25 are required to stabilize the capsid shells at the vertices. This indicates that herpesviruses withstand the internal pressure that is generated during DNA genome packaging by locally reinforcing the mechanical sturdiness of the vertices, the most stressed part of the capsids.IMPORTANCEIn this study, the structural, material properties of herpes simplex virus 1 were investigated. The capsid of herpes simplex virus is built up of a variety of proteins, and we scrutinized the influence of two of these proteins on the stability of the capsid. For this, we used a scanning force microscope that makes detailed, topographic images of the particles and that is able to perform mechanical deformation measurements. Using this approach, we revealed that both studied proteins play an essential role in viral stability. These new insights support us in forming a complete view on viral structure and furthermore could possibly help not only to develop specific antivirals but also to build protein shells with improved stability for drug delivery purposes.
authors.affiliation: Natuur- en Sterrenkunde & LaserLab, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Snijder
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Kerstin
authors.initials: K
authors.lastname: Radtke
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany.
authors.forename: Fenja
authors.initials: F
authors.lastname: Anderson
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
authors.forename: Luella
authors.initials: L
authors.lastname: Scholtes
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Netherlands Proteomics Centre, Utrecht, The Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Corradini
authors.affiliation: Department of Microbiology and Immunology, Cornell University, Ithaca, New York, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Baines
authors.affiliation: Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research and Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Netherlands Proteomics Centre, Utrecht, The Netherlands.
authors.forename: Albert J R
authors.initials: AJR
authors.lastname: Heck
authors.affiliation: Natuur- en Sterrenkunde & LaserLab, Vrije Universiteit, Amsterdam, The Netherlands.
authors.forename: Gijs J L
authors.initials: GJL
authors.lastname: Wuite
authors.affiliation: Institute of Virology, Hannover Medical School, Hannover, Germany Sodeik.Beate@mh-hannover.de w.h.roos@rug.nl.|German Centre for Infection Research (DZIF), Hannover, Germany.
authors.forename: Beate
authors.initials: B
authors.lastname: Sodeik
authors.affiliation: Natuur- en Sterrenkunde & LaserLab, Vrije Universiteit, Amsterdam, The Netherlands Sodeik.Beate@mh-hannover.de w.h.roos@rug.nl.|Moleculaire Biofysica, Zernike Instituut, Rijksuniversiteit Groningen, Groningen, The Netherlands.
authors.forename: Wouter H
authors.initials: WH
authors.lastname: Roos
mesh_terms: D002213:Capsid / Q000737:chemistry*; D036022:Capsid Proteins / Q000502:physiology*; D002460:Cell Line; D042003:DNA Packaging; D018259:Herpesvirus 1, Human / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D013058:Mass Spectrometry; D018625:Microscopy, Atomic Force; D011485:Protein Binding; D014763:Viral Matrix Proteins / Q000378:metabolism; D019065:Virus Assembly
chemical_list: D036022:Capsid Proteins; D014763:Viral Matrix Proteins
keywords: AFM; capsid; herpes simplex virus; stability