Journal Article

PUBDB-2026-01362

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png The MHV-68 nuclear egress complex supports C-capsid selective capsid egress

Sanders, S.Extern*CSSB* ; Schneider, C. ; Soh, T. K. ; Kotova, E.Extern*CSSB* ; Stalling, D. ; Steer, B. ; Reimer, R. ; Ruzsics, Z. ; Adler, H. (Corresponding author) ; Bosse, J. B. (Corresponding author)Extern*CSSB*

2026
Soc. Baltimore, Md.

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Please use a persistent id in citations: doi:10.1128/jvi.00072-26  doi:10.3204/PUBDB-2026-01362

Abstract: Herpesvirus capsids assemble within the host nucleus and must traverse the nuclear envelope to undergo final envelopment in the cytoplasm. This exit strategy is orchestrated by the nuclear egress complex (NEC), a conserved heterodimeric protein complex that forms lattices that remodel the inner nuclear membrane. While the NEC is critical for efficient replication across α-, β-, and γ-herpesviruses, residual infectivity has been noted in NEC-deficient mutants of the ɑ-herpesvirus Pseudorabies virus. Here, we investigated the NEC’s role in the γ-herpesvirus murine γ-herpesvirus 68 (MHV-68) by generating a mutant virus (ΔC-ORF69) lacking the majority of the nucleoplasmic NEC component, ORF69. Unlike prior studies utilizing transfection-based systems, we demonstrate that NEC-deficient MHV-68 produces infectious progeny in non-complementing cells, albeit with a significant replication defect. Quantitative electron microscopy confirmed that while nuclear capsid assembly remained regular, the canonical export mechanism was abolished. Whereas the parental virus predominantly exported mature, enveloped, genome-filled C-capsids out of the nucleus, the ΔC-ORF69 mutant released all major capsid forms (A, B, and C) into the cytoplasm and extracellular space, associated with loss of nuclear integrity. These findings suggest that, in addition to mediating efficient capsid translocation across the nuclear envelope, the MHV-68 NEC imposes C-capsid selectivity during nuclear egress, thereby acting as a quality control checkpoint. Inhibition of cyclin-dependent kinases reduced viral spread in both parental and ΔC-ORF69 viruses, indicating that cyclin-dependent kinase activity contributes to productive infection and may influence the residual spread observed in ΔC-ORF69, consistent with a potential contribution to late-stage nuclear envelope integrity loss.

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Contributing Institute(s):

1. CSSB-MHH-JB (CSSB-MHH-JB)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)
2. DFG project G:(GEPRIS)390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)
3. GRK 2771 - GRK 2771: Mensch und Mikrobe: Reorganisation von Zellkompartimenten und Molekülkomplexen während der Infektion (453548970) (453548970)
4. DFG project G:(GEPRIS)443644894 - FOR 5200: Disrupt - Evade - Exploit: Steuerung der Genexpression und Wirtsantwort durch DNA Viren (DEEP-DV) (443644894) (443644894)
5. DFG project G:(GEPRIS)512741711 - SFB 1648: Neu auftretende Viren: Pathogenese, Struktur und Immunität (512741711) (512741711)

Experiment(s):

1. (Advanced Light and Fluorescence Microscopy Facility)

Appears in the scientific report 2026

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Database coverage:
; ; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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