Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication

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...

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Main Authors: Lady S. López, Eliana P. Calvo, Jaime E. Castellanos
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:Viruses
Subjects:
Online Access:https://www.mdpi.com/1999-4915/15/2/481
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author Lady S. López
Eliana P. Calvo
Jaime E. Castellanos
author_facet Lady S. López
Eliana P. Calvo
Jaime E. Castellanos
author_sort Lady S. López
collection DOAJ
description 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.
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spelling doaj.art-344aa8243a0f4cb395d8b65120783bbc2023-11-16T23:49:36ZengMDPI AGViruses1999-49152023-02-0115248110.3390/v15020481Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus ReplicationLady S. López0Eliana P. Calvo1Jaime E. Castellanos2Grupo de Virología, Universidad El Bosque, Bogotá 110121, ColombiaGrupo de Virología, Universidad El Bosque, Bogotá 110121, ColombiaGrupo de Virología, Universidad El Bosque, Bogotá 110121, ColombiaUbiquitination 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.https://www.mdpi.com/1999-4915/15/2/481chikungunya virusinfectionreplicationubiquitinationdeubiquitinating enzymesdeubiquitinase inhibitor
spellingShingle Lady S. López
Eliana P. Calvo
Jaime E. Castellanos
Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
Viruses
chikungunya virus
infection
replication
ubiquitination
deubiquitinating enzymes
deubiquitinase inhibitor
title Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
title_full Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
title_fullStr Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
title_full_unstemmed Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
title_short Deubiquitinating Enzyme Inhibitors Block Chikungunya Virus Replication
title_sort deubiquitinating enzyme inhibitors block chikungunya virus replication
topic chikungunya virus
infection
replication
ubiquitination
deubiquitinating enzymes
deubiquitinase inhibitor
url https://www.mdpi.com/1999-4915/15/2/481
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AT jaimeecastellanos deubiquitinatingenzymeinhibitorsblockchikungunyavirusreplication