Multi-protomics analysis identified host cellular pathways perturbed by tick-borne encephalitis virus infection.

Area of Science:

• Virology
• Molecular Biology
• Immunology

Background:

• Tick-borne encephalitis virus (TBEV) causes severe neurological illness in Europe and Asia.
• Emerging mutations, vaccine breakthroughs, and lack of treatments for related flaviviruses necessitate understanding TBEV pathogenesis.

Purpose of the Study:

• To elucidate cellular proteome, phosphoproteome, and acetylproteome changes during TBEV infection.
• To identify host pathways and viral mechanisms involved in TBEV pathogenesis.
• To explore potential antiviral intervention targets.

Main Methods:

• Proteomic, phosphoproteomic, and acetylproteomic analyses of TBEV-infected cells.
• Investigation of viral protein interactions with host factors (NS5, prM with SIRT1, KAP1, Ku70, AKT1, VPS11).
• Assessment of antiviral activity of DDR and kinase inhibitors.

Main Results:

• TBEV infection significantly impacts innate immunity, ribosomal biogenesis, autophagy, and DNA damage response (DDR).
• TBEV NS5 protein inhibits DNA repair by suppressing KAP1 and Ku70 deacetylation via SIRT1 interaction.
• TBEV prM protein induces autophagy via AKT1 but hinders autolysosome formation by binding VPS11.

Conclusions:

• TBEV manipulates host cellular pathways, including autophagy and DDR, for its replication.
• Dysregulated pathways and kinases identified are potential targets for antiviral therapies.
• Findings provide insights for developing effective treatments against TBEV and other tick-borne flaviviruses.