Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication

Autores organización

• 

  Eliana Patricia Calvo Tapiero

  Autor

• 

  Jaime Eduardo Castellanos Parra

  Autor

Autores

• López L.S.

Grupos de investigación

• Grupo de Virología

  

  Investigador

  Jaime Eduardo Castellanos Parra

Resumen

Ubiquitination and deubiquitination processes are widely involved in modulating the function, activity, localization, and stability of multiple cellular proteins regulating almost every aspect of cellular function. Several virus families have been shown to exploit the cellular ubiquitin-conjugating system to achieve a productive infection: enter the cell, promote genome replication, or assemble and release viral progeny. In this study, we analyzed the role of deubiquitinating enzymes (DUBs) during chikungunya virus (CHIKV) infection. HEK293T, Vero-E6, and Huh-7 cells were treated with two DUB inhibitors (PR619 or WP1130). Then, infected cells were evaluated by flow cytometry, and viral progeny was quantified using the plaque assay method. The changes in viral proteins and viral RNA were analyzed using Western blotting and RT-qPCR, respectively. Results indicate that treatment with DUB inhibitors impairs CHIKV replication due to significant protein and viral RNA synthesis deregulation. Therefore, DUB activity may be a pharmacological target for blocking CHIKV infection. © 2023 by the authors.

Keywords

• Chikungunya Fever; Chikungunya virus; Deubiquitinating Enzymes; Enzyme Inhibitors; HEK293 Cells; Humans; RNA, Viral; enzyme inhibitor; viral protein; virus RNA; deubiquitinase; enzyme inhibitor; antigen detection; Article; BHK-21 cell line; cell viability; cell viability assay; Chikungunya virus; deubiquitination; flow cytometry; HEK293 cell line; Huh-7 cell line; human; human cell; protein analysis; protein localization; protein stability; real time polymerase chain reaction; Vero C1008 cell line; viral plaque assay; virus infection; virus replication; virus titration; Western blotting; chikungunya