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TitleCryogenic Electron Tomography Redefines Herpesvirus Capsid Assembly Intermediates Inside the Cell Nucleus.
Journal, issue, pagesbioRxiv, Year 2025
Publish dateJun 28, 2025
AuthorsStefan L Oliver / Muyuan Chen / Leeya Engel / Corey W Hecksel / Xueting Zhou / Michael F Schmid / Ann M Arvin / Wah Chiu
PubMed AbstractHerpesviruses encapsulate their double-stranded DNA (dsDNA) genomes within an icosahedral nucleocapsid formed in the infected cell nucleus. Four biochemically purified nucleocapsids have been ...Herpesviruses encapsulate their double-stranded DNA (dsDNA) genomes within an icosahedral nucleocapsid formed in the infected cell nucleus. Four biochemically purified nucleocapsids have been characterized, but their roles in herpesvirus replication remain controversial. The status of the capsid vertex-specific component (CVSC), essential for capsid stability and dsDNA packaging and retention, is also unclear. By integrating cryogenic focused ion beam milling with electron tomography and subtomogram averaging, we derived atomic models for all protein components, including the CVSC, across different herpesvirus capsid types within infected cell nuclei. Focused classification of pentonal vertex densities revealed differences in CVSC occupancy between genome-filled capsids and capsids lacking dsDNA, highlighting structural heterogeneity and providing insight into distinct capsid assembly stages . These intra-nuclear findings redefine the maturation model of herpesvirus capsid assembly, advancing the understanding of herpesvirus replication, and demonstrate the effectiveness of electron imaging by studying virus assembly within host cells.
External linksbioRxiv / PubMed:40666836 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution8.3 Å
Structure data

49591

9no1

EMDB-49591, PDB-9no1:
Cryo-ET map of the VZV capsid vertex (5-fold axis).
Method: EM (subtomogram averaging) / Resolution: 8.3 Å

Source
  • human alphaherpesvirus 3 (Varicella-zoster virus)
KeywordsVIRUS / Varicella-zoster virus / capsid / cryo-ET / cryo-FIB

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