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TitleCryogenic electron tomography reveals herpesvirus capsid assembly intermediates inside the cell nucleus.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateFeb 25, 2026
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 derive atomic models for all protein components, including the CVSC, across different herpesvirus capsid types within infected cell nuclei. Focused classification of pentonal vertex densities reveal differences in CVSC occupancy between genome-filled capsids and capsids lacking dsDNA, highlight structural heterogeneity and providing insight into distinct capsid assembly stages in situ. These intra-nuclear findings redefine the maturation model of herpesvirus capsid assembly, advancing the understanding of herpesvirus replication, and demonstrate the effectiveness of in situ electron imaging by studying virus assembly within host cells.
External linksNat Commun / PubMed:41741463 / PubMed Central
MethodsEM (subtomogram averaging)
Resolution8.3 - 33.6 Å
Structure data

EMDB-49465: Reconstruction of the intranuclear varicella-zoster virus capsid.
Method: EM (subtomogram averaging) / Resolution: 12.1 Å

EMDB-49466: Reconstruction of the varicella-zoster virus capsid vertex.
Method: EM (subtomogram averaging) / Resolution: 10.3 Å

EMDB-49467: Reconstruction of the intracellular varicella-zoster virus capsid with portal.
Method: EM (subtomogram averaging) / Resolution: 24.5 Å

EMDB-49468: VZV portal vertex cryo-ET reconstruction.
Method: EM (subtomogram averaging) / Resolution: 23.6 Å

EMDB-49469: VZV portal cryo-ET reconstruction.
Method: EM (subtomogram averaging) / Resolution: 22.9 Å

EMDB-49470: Reconstruction of intracellular varicella zoster virus CAI-capsid with portal.
Method: EM (subtomogram averaging) / Resolution: 32.6 Å

EMDB-49471: Reconstruction of the portal vertex from intracellular varicella-zoster virus CAI-capsids.
Method: EM (subtomogram averaging) / Resolution: 23.8 Å

EMDB-49472: Reconstruction of the varicella-zoster virus C-capsid with the portal vertex.
Method: EM (subtomogram averaging) / Resolution: 33.6 Å

EMDB-49473: VZV C-capsid portal vertex.
Method: EM (subtomogram averaging) / Resolution: 24.3 Å

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

EMDB-49886: Cryo-ET map of the VZV capsid 3-fold axis.
Method: EM (subtomogram averaging) / Resolution: 8.4 Å

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

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