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Title | Molecular plasticity of herpesvirus nuclear egress analysed in situ. |
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Journal, issue, pages | Nat Microbiol, Vol. 9, Issue 7, Page 1842-1855, Year 2024 |
Publish date | Jun 25, 2024 |
Authors | Vojtěch Pražák / Yuliia Mironova / Daven Vasishtan / Christoph Hagen / Ulrike Laugks / Yannick Jensen / Saskia Sanders / John M Heumann / Jens B Bosse / Barbara G Klupp / Thomas C Mettenleiter / Michael Grange / Kay Grünewald / |
PubMed Abstract | The viral nuclear egress complex (NEC) allows herpesvirus capsids to escape from the nucleus without compromising the nuclear envelope integrity. The NEC lattice assembles on the inner nuclear ...The viral nuclear egress complex (NEC) allows herpesvirus capsids to escape from the nucleus without compromising the nuclear envelope integrity. The NEC lattice assembles on the inner nuclear membrane and mediates the budding of nascent nucleocapsids into the perinuclear space and their subsequent release into the cytosol. Its essential role makes it a potent antiviral target, necessitating structural information in the context of a cellular infection. Here we determined structures of NEC-capsid interfaces in situ using electron cryo-tomography, showing a substantial structural heterogeneity. In addition, while the capsid is associated with budding initiation, it is not required for curvature formation. By determining the NEC structure in several conformations, we show that curvature arises from an asymmetric assembly of disordered and hexagonally ordered lattice domains independent of pUL25 or other viral capsid vertex components. Our results advance our understanding of the mechanism of nuclear egress in the context of a living cell. |
External links | Nat Microbiol / PubMed:38918469 / PubMed Central |
Methods | EM (subtomogram averaging) |
Resolution | 14.0 - 38.0 Å |
Structure data | EMDB-17974: Pseudorabies virus cytosolic C-capsid (US3 KO) vertices determined in situ EMDB-17975: Pseudorabies virus primary enveloped (perinuclear) C-capsid (US3 KO) vertices determined in situ EMDB-17976: Pseudorabies nuclear C-capsids (US3 KO) vertices determined in situ EMDB-18473: Subtomogram average of pseudorabies virus nuclear egress complex helical form (UL31/34) determined in situ EMDB-18474: Subtomogram average of pseudorabies virus nuclear egress complex (UL31/34) determined in situ EMDB-18479: Pseudorabies virus cytosolic C-capsid (WT) vertices determined in situ EMDB-18480: Pseudorabies virus nuclear C-capsid (WT) vertices determined in situ EMDB-18481: Herpes simplex virus 1 cytosolic C-capsid (WT) vertices determined in situ EMDB-18482: Herpes simplex virus 1 capsid (WT) vertices in perinuclear NEC-coated vesicles determined in situ EMDB-18483: Herpes simplex virus 1 nuclear C-capsid (WT) vertices determined in situ EMDB-18484: Herpes simplex virus 1 nuclear egress complex (WT) determined in situ from perinuclear vesicles |
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