The 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 the icosahedral Herpes Simplex Virus capsids. pUL17 and pUL25 that form the capsid vertex-specific component (CVSC) particularly contributed to the capsid resilience along the 5-fold and 2-fold, but not along the 3-fold icosahedral axes. Our detailed analyses, including quantitative mass spectrometry on the protein composition of the capsids, revealed that pUL17 and pUL25 are both 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.IMPORTANCE In this study the structural, material properties of Herpes Simplex Virus type 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 to form a complete view on viral structure and could furthermore possibly not only help to develop specific anti-virals, but also to build protein shells with improved stability for drug delivery purposes.