| Title: |
Multi-proteomic profiling of the varicella-zoster virus–host interface reveals host susceptibilities to severe infection |
| Authors: |
Girault, V; Stukalov, A; Carter-Timofte, ME; Hertzog, J; Verin, M; Austen, K; Haas, DA; Oubraham, L; Piras, A; Maidl, S; Öllinger, R; Rad, R; Protzer, U; Kaufer, BB; Lebbink, RJ; Rehwinkel, J; Mogensen, TH; Pichlmair, A |
| Publisher Information: |
Nature Research |
| Publication Year: |
2025 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s41564-025-02068-7 |
| Availability: |
https://doi.org/10.1038/s41564-025-02068-7; https://ora.ox.ac.uk/objects/uuid:2f614f71-e6a2-4e29-a57a-2c8dc09033ae |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution (CC BY) |
| Accession Number: |
edsbas.C1188147 |
| Database: |
BASE |