Multi-omics characterization of the monkeypox virus infection

Area of Science:

• Virology
• Molecular Biology
• Systems Biology

Background:

• Vaccinia virus (VACV) has been extensively studied, but the molecular mechanisms of monkeypox virus (MPXV) infection in humans remain largely unknown.
• Despite high sequence similarity, MPXV exhibits different disease manifestations compared to VACV.

Purpose of the Study:

• To perform a comprehensive multi-omics analysis (transcriptome, proteome, phosphoproteome) of MPXV-infected human fibroblasts.
• To elucidate the virus-host interplay and identify key signaling pathways and molecular targets during MPXV infection.

Main Methods:

• In-depth multi-omics analysis of MPXV-infected primary human fibroblasts.
• Integrated pathway analysis and drug-target prediction.
• Functional validation of identified drug targets against MPXV and VACV.

Main Results:

• MPXV infection perturbs immune-related pathways and regulates HIPPO and TGF-β signaling.
• Dynamic phosphorylation of host and viral proteins was observed, with MAPKs identified as key regulators.
• Phosphorylation of viral protein H5 was found to influence its dsDNA binding.
• Potential drug targets including MTOR, CHUK/IKBKB, and splicing factor kinases were identified.

Conclusions:

• This study provides an extensive dataset on MPXV-induced signaling events, expanding knowledge of poxvirus biology.
• Identified drug targets demonstrate potent antiviral efficacy against both MPXV and VACV, suggesting broad applicability.
• The findings pave the way for developing novel therapeutic strategies against poxvirus infections.