Multi-omics characterization of the monkeypox virus infection

Yiqi Huang, Valter Bergant, Vincent Grass, Quirin Emslander, M. Sabri Hamad, Philipp Hubel, Julia Mergner, Antonio Piras, Karsten Krey, Alexander Henrici, Rupert Öllinger, Yonas M. Tesfamariam, Ilaria Dalla Rosa, Till Bunse, Gerd Sutter, Gregor Ebert, Florian I. Schmidt, Michael Way, Roland Rad, Andrew G. Bowie, Ulrike Protzer and Andreas Pichlmair ()
Additional contact information
Yiqi Huang: School of Medicine
Valter Bergant: School of Medicine
Vincent Grass: School of Medicine
Quirin Emslander: School of Medicine
M. Sabri Hamad: School of Medicine
Philipp Hubel: Max-Planck Institute of Biochemistry
Julia Mergner: Technical University of Munich
Antonio Piras: School of Medicine
Karsten Krey: School of Medicine
Alexander Henrici: School of Medicine
Rupert Öllinger: Technical University of Munich
Yonas M. Tesfamariam: University of Bonn
Ilaria Dalla Rosa: The Francis Crick Institute
Till Bunse: School of Medicine
Gerd Sutter: LMU Munich
Gregor Ebert: School of Medicine/Helmholtz Munich
Florian I. Schmidt: University of Bonn
Michael Way: The Francis Crick Institute
Roland Rad: Technical University of Munich
Andrew G. Bowie: Trinity College Dublin
Ulrike Protzer: Partner site Munich
Andreas Pichlmair: School of Medicine

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-51074-6 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-51074-6

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-51074-6

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().