Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication

Viruses. 2023 Feb 9;15(2):481. doi: 10.3390/v15020481.

Abstract

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.

Keywords: chikungunya virus; deubiquitinase inhibitor; deubiquitinating enzymes; infection; replication; ubiquitination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chikungunya Fever* / drug therapy
  • Chikungunya virus* / drug effects
  • Deubiquitinating Enzymes* / antagonists & inhibitors
  • Enzyme Inhibitors* / pharmacology
  • Enzyme Inhibitors* / therapeutic use
  • HEK293 Cells
  • Humans
  • RNA, Viral
  • Virus Replication* / drug effects

Substances

  • Deubiquitinating Enzymes
  • Enzyme Inhibitors
  • RNA, Viral

Grants and funding

This project was funded by Ministerio de Ciencia y Tecnología de Colombia Grant Number: 130871250759 and Vicerrectoría de Investigaciones-Universidad El Bosque Project 702487.