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Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
Lady S López1, Eliana P Calvo1, Jaime E Castellanos1
1Grupo de Virología, Universidad El Bosque, Bogotá 110121, Colombia.
Viruses
|February 28, 2023
Summary
Deubiquitinating enzymes (DUBs) are crucial for cellular protein regulation. Inhibiting DUBs significantly disrupts chikungunya virus (CHIKV) replication by affecting viral protein and RNA synthesis, suggesting DUBs as a potential therapeutic target.
Area of Science:
- Molecular Biology
- Virology
- Biochemistry
Background:
- Ubiquitination and deubiquitination are vital post-translational modifications regulating protein function and stability.
- Viruses often hijack cellular ubiquitin systems for their replication cycles.
- Deubiquitinating enzymes (DUBs) play a critical role in cellular processes and viral infections.
Purpose of the Study:
- To investigate the role of DUBs in chikungunya virus (CHIKV) infection.
- To determine if DUB inhibition can impede CHIKV replication.
Main Methods:
- HEK293T, Vero-E6, and Huh-7 cells were treated with DUB inhibitors (PR619 or WP1130).
- Viral replication was assessed using flow cytometry and plaque assays.
- Viral protein and RNA levels were quantified via Western blotting and RT-qPCR.
Main Results:
- DUB inhibition significantly impaired CHIKV replication in treated cells.
- Treatment led to deregulation of viral protein and viral RNA synthesis.
- Flow cytometry, plaque assays, Western blotting, and RT-qPCR confirmed reduced viral load.
Conclusions:
- DUB activity is essential for efficient CHIKV replication.
- Inhibiting DUBs presents a potential therapeutic strategy against CHIKV infection.
- Targeting DUBs could be a novel pharmacological approach to block chikungunya virus proliferation.
