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Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy

Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study,...

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Detalles Bibliográficos
Autores principales: Zhou, Fanghang, Wan, Qianya, Lu, Jing, Chen, Ying, Lu, Gui, He, Ming-Liang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726883/
https://www.ncbi.nlm.nih.gov/pubmed/31476618
http://dx.doi.org/10.1016/j.isci.2019.08.008
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author Zhou, Fanghang
Wan, Qianya
Lu, Jing
Chen, Ying
Lu, Gui
He, Ming-Liang
author_facet Zhou, Fanghang
Wan, Qianya
Lu, Jing
Chen, Ying
Lu, Gui
He, Ming-Liang
author_sort Zhou, Fanghang
collection PubMed
description Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment.
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spelling pubmed-67268832019-09-10 Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy Zhou, Fanghang Wan, Qianya Lu, Jing Chen, Ying Lu, Gui He, Ming-Liang iScience Article Enterovirus A71 (EV-A71) infection causes hand-foot-and-mouth disease (HFMD) and fatal neurological diseases, and there are no effective treatments. Host factors play key roles in establishing viral infection and determining the disease progression and outcome of antiviral therapies. In this study, we found that the expression of Pim1 was significantly upregulated in EV-A71 infection. Ectopic expression or silencing of Pim1 promoted or inhibited EV-A71 replication through two distinct mechanisms. Pim1 enhanced viral IRES activity by increasing viral 2A protease-mediated eIF4G cleavage and blocked AUF1, a suppressor of IRES, translocation from the nucleus to cytosol. More importantly, we discovered that Pim1 inhibitors (SGI-1776, AZD-1208, and CX-6258) reduced EV-A71 reproduction. Particularly, CX-6258 remarkably reduced EV-A71 reproduction more than 1,000 times, providing a potential therapeutic agent for EV-A71 treatment. Elsevier 2019-08-08 /pmc/articles/PMC6726883/ /pubmed/31476618 http://dx.doi.org/10.1016/j.isci.2019.08.008 Text en © 2019 The Authors http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Article
Zhou, Fanghang
Wan, Qianya
Lu, Jing
Chen, Ying
Lu, Gui
He, Ming-Liang
Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy
title Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy
title_full Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy
title_fullStr Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy
title_full_unstemmed Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy
title_short Pim1 Impacts Enterovirus A71 Replication and Represents a Potential Target in Antiviral Therapy
title_sort pim1 impacts enterovirus a71 replication and represents a potential target in antiviral therapy
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6726883/
https://www.ncbi.nlm.nih.gov/pubmed/31476618
http://dx.doi.org/10.1016/j.isci.2019.08.008
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