Multi-omics characterization of the monkeypox virus infection.

Humans Monkeypox virus / genetics Phosphorylation Mpox (monkeypox) / virology Fibroblasts / virology Viral Proteins / metabolism Proteome / metabolism Host-Pathogen Interactions Signal Transduction Proteomics / methods Transcriptome Antiviral Agents / pharmacology Multiomics

Journal

Nature communications

ISSN: 2041-1723

Titre abrégé: Nat Commun

Pays: England

ID NLM: 101528555

Informations de publication

Date de publication:
08 Aug 2024

Historique:

received: 19 12 2023

accepted: 26 07 2024

medline: 9 8 2024

pubmed: 9 8 2024

entrez: 8 8 2024

Statut: epublish

Résumé

Multiple omics analyzes of Vaccinia virus (VACV) infection have defined molecular characteristics of poxvirus biology. However, little is known about the monkeypox (mpox) virus (MPXV) in humans, which has a different disease manifestation despite its high sequence similarity to VACV. Here, we perform an in-depth multi-omics analysis of the transcriptome, proteome, and phosphoproteome signatures of MPXV-infected primary human fibroblasts to gain insights into the virus-host interplay. In addition to expected perturbations of immune-related pathways, we uncover regulation of the HIPPO and TGF-β pathways. We identify dynamic phosphorylation of both host and viral proteins, which suggests that MAPKs are key regulators of differential phosphorylation in MPXV-infected cells. Among the viral proteins, we find dynamic phosphorylation of H5 that influenced the binding of H5 to dsDNA. Our extensive dataset highlights signaling events and hotspots perturbed by MPXV, extending the current knowledge on poxviruses. We use integrated pathway analysis and drug-target prediction approaches to identify potential drug targets that affect virus growth. Functionally, we exemplify the utility of this approach by identifying inhibitors of MTOR, CHUK/IKBKB, and splicing factor kinases with potent antiviral efficacy against MPXV and VACV.

Identifiants

DOI: 10.1038/s41467-024-51074-6 PMID: 39117661

pubmed: 39117661

doi: 10.1038/s41467-024-51074-6

pii: 10.1038/s41467-024-51074-6

doi:

Substances chimiques

Viral Proteins 0

Proteome 0

Antiviral Agents 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

Pagination

6778

Subventions

Organisme : Deutsche Forschungsgemeinschaft (German Research Foundation)

ID : TRR179-272983813, TRR237-369799452, TRR353-471011418, INST 95/1650-1

Organisme : Helmholtz Association

ID : KA1-Co-02

Informations de copyright

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