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Girault, V.* ; Stukalov, A.* ; Carter-Timofte, M.E.* ; Hertzog, J.* ; Verin, M. ; Austen, K.* ; Haas, D.A.* ; Oubraham, L.* ; Piras, A.* ; Maidl, S.* ; Öllinger, R.* ; Rad, R.* ; Protzer, U.* ; Kaufer, B.B.* ; Lebbink, R.J.* ; Rehwinkel, J.* ; Mogensen, T.H.* ; Pichlmair, A.

Multi-proteomic profiling of the varicella-zoster virus-host interface reveals host susceptibilities to severe infection.

Nat. Microbiol. 10, 2048-2072 (2025)
Publ. Version/Full Text Research data DOI PMC
Open Access Hybrid
Creative Commons Lizenzvertrag
Varicella-zoster virus (VZV) infects most humans and causes chickenpox, shingles and central nervous system pathologies. The molecular basis for these phenotypes remains elusive. Here we conducted a multi-proteomic survey on 64 individual VZV proteins and infection-induced perturbations in a neuronal cell line, identifying 900 interactors and 3,618 regulated host proteins. Data integration suggested molecular functions of viral proteins, such as a mechanism for the ORF61-mediated IFI16 degradation via the recruitment of E3 ligase co-factors. Moreover, we identified proviral host factors (MPP8 and ZNF280D) as potential targets to limit infection. Integration of exome sequencing analysis from patients with VZV-associated central nervous system pathologies identified nephrocystin 4 as a viral restriction factor, and its S862N variant, which showed reduced activity and decreased binding to the regulatory proteins 14-3-3. Collectively, our study provides a comprehensive herpesvirus-host interface resource, which aids our understanding of disease-associated molecular perturbations and data-driven identification of antiviral treatment options.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Herpes-simplex-virus; Essential Tegument Protein; Mediator Complex; Ie63 Protein; Interacts; Cells; Vzv; Localization; Replication; Resistance
Language english
Publication Year 2025
HGF-reported in Year 2025
ISSN (print) / ISBN 2058-5276
e-ISSN 2058-5276
Journal Nature microbiology
Quellenangaben Volume: 10, Issue: 8, Pages: 2048-2072 Article Number: , Supplement: ,
Publisher Nature Publishing Group
Publishing Place London
Reviewing status Peer reviewed
Institute(s) Institute of Virology (VIRO)
POF-Topic(s) 30203 - Molecular Targets and Therapies
Research field(s) Immune Response and Infection
PSP Element(s) G-502700-003
Grants
German Federal Ministry of Education and Research
Independent Research Fund Denmark
The 'COVIPA' consortium (Helmholtz Association's Initiative and Networking Fund)
Danish National Research Foundation
ERC
Marie Sklodowska-Curie Actions-Innovative Training Networks Programme
European Union under the Horizon 2020 Research and Innovation program
TUM Innovation Network NextGenDrugs funded under the Excellence Strategy of the Federal Government
Wellcome Trust
MRC Human Immunology Unit
UK Medical Research Council (MRC)
Federal Ministry of Science and Education (BMBF)
State of Bavaria
German Research Foundation
Technische Universität München
DOI 10.1038/s41564-025-02068-7
WOS ID 001539882000001
Scopus ID 105012292988
PubMed ID 40739040
Erfassungsdatum 2025-08-01
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