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USP18 Mediates Interferon Resistance of Dengue Virus Infection
Previous studies demonstrated that dengue virus (DENV) infection developed resistance to type-I interferons (IFNα/β). The underlying mechanism remains unclear. USP18 is a negative regulator of IFNα/β signaling, and its expression level is significantly increased following DENV infection in cell line...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130619/ https://www.ncbi.nlm.nih.gov/pubmed/34017322 http://dx.doi.org/10.3389/fmicb.2021.682380 |
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author | Ye, Haiyan Duan, Xiaoqiong Yao, Min Kang, Lan Li, Yujia Li, Shilin Li, Bin Chen, Limin |
author_facet | Ye, Haiyan Duan, Xiaoqiong Yao, Min Kang, Lan Li, Yujia Li, Shilin Li, Bin Chen, Limin |
author_sort | Ye, Haiyan |
collection | PubMed |
description | Previous studies demonstrated that dengue virus (DENV) infection developed resistance to type-I interferons (IFNα/β). The underlying mechanism remains unclear. USP18 is a negative regulator of IFNα/β signaling, and its expression level is significantly increased following DENV infection in cell lines and patients’ blood. Our previous study revealed that increased USP18 expression contributed to the IFN-α resistance of Hepatitis C Virus (HCV). However, the role of USP18 in DENV replication and resistance to IFN-α is elusive. In this current study, we aimed to explore the role of USP18 in DENV-2 replication and resistance to IFN-α. The level of USP18 was up-regulated by plasmid transfection and down-regulated by siRNA transfection in Hela cells. USP18, IFN-α, IFN-β expression, and DENV-2 replication were monitored by qRT-PCR and Western blot. The activation of the Jak/STAT signaling pathway was assessed at three levels: p-STAT1/p-STAT2 (Western blot), interferon-stimulated response element (ISRE) activity (Dual-luciferase assay), and interferon-stimulated genes (ISGs) expression (qRT-PCR). Our data showed that DENV-2 infection increased USP18 expression in Hela cells. USP18 overexpression promoted DENV-2 replication, while USP18 silence inhibited DENV-2 replication. Silence of USP18 potentiated the anti-DENV-2 activity of IFN-α through activation of the IFN-α-mediated Jak/STAT signaling pathway as shown by increased expression of p-STAT1/p-STAT2, enhanced ISRE activity, and elevated expression of some ISGs. Our data indicated that USP18 induced by DENV-2 infection is a critical host factor utilized by DENV-2 to confer antagonism on IFN-α. |
format | Online Article Text |
id | pubmed-8130619 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-81306192021-05-19 USP18 Mediates Interferon Resistance of Dengue Virus Infection Ye, Haiyan Duan, Xiaoqiong Yao, Min Kang, Lan Li, Yujia Li, Shilin Li, Bin Chen, Limin Front Microbiol Microbiology Previous studies demonstrated that dengue virus (DENV) infection developed resistance to type-I interferons (IFNα/β). The underlying mechanism remains unclear. USP18 is a negative regulator of IFNα/β signaling, and its expression level is significantly increased following DENV infection in cell lines and patients’ blood. Our previous study revealed that increased USP18 expression contributed to the IFN-α resistance of Hepatitis C Virus (HCV). However, the role of USP18 in DENV replication and resistance to IFN-α is elusive. In this current study, we aimed to explore the role of USP18 in DENV-2 replication and resistance to IFN-α. The level of USP18 was up-regulated by plasmid transfection and down-regulated by siRNA transfection in Hela cells. USP18, IFN-α, IFN-β expression, and DENV-2 replication were monitored by qRT-PCR and Western blot. The activation of the Jak/STAT signaling pathway was assessed at three levels: p-STAT1/p-STAT2 (Western blot), interferon-stimulated response element (ISRE) activity (Dual-luciferase assay), and interferon-stimulated genes (ISGs) expression (qRT-PCR). Our data showed that DENV-2 infection increased USP18 expression in Hela cells. USP18 overexpression promoted DENV-2 replication, while USP18 silence inhibited DENV-2 replication. Silence of USP18 potentiated the anti-DENV-2 activity of IFN-α through activation of the IFN-α-mediated Jak/STAT signaling pathway as shown by increased expression of p-STAT1/p-STAT2, enhanced ISRE activity, and elevated expression of some ISGs. Our data indicated that USP18 induced by DENV-2 infection is a critical host factor utilized by DENV-2 to confer antagonism on IFN-α. Frontiers Media S.A. 2021-04-30 /pmc/articles/PMC8130619/ /pubmed/34017322 http://dx.doi.org/10.3389/fmicb.2021.682380 Text en Copyright © 2021 Ye, Duan, Yao, Kang, Li, Li, Li and Chen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Ye, Haiyan Duan, Xiaoqiong Yao, Min Kang, Lan Li, Yujia Li, Shilin Li, Bin Chen, Limin USP18 Mediates Interferon Resistance of Dengue Virus Infection |
title | USP18 Mediates Interferon Resistance of Dengue Virus Infection |
title_full | USP18 Mediates Interferon Resistance of Dengue Virus Infection |
title_fullStr | USP18 Mediates Interferon Resistance of Dengue Virus Infection |
title_full_unstemmed | USP18 Mediates Interferon Resistance of Dengue Virus Infection |
title_short | USP18 Mediates Interferon Resistance of Dengue Virus Infection |
title_sort | usp18 mediates interferon resistance of dengue virus infection |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8130619/ https://www.ncbi.nlm.nih.gov/pubmed/34017322 http://dx.doi.org/10.3389/fmicb.2021.682380 |
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