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Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells
BACKGROUND: Promyelocytic leukemia protein (PML) is a primary component of PML nuclear bodies (PML-NBs). PML and PML-NBs play critical roles in processes like the cell cycle, DNA damage repair, apoptosis, and the antiviral immune response. Previously, we identified five porcine PML alternative splic...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687900/ https://www.ncbi.nlm.nih.gov/pubmed/38031162 http://dx.doi.org/10.1186/s12985-023-02212-x |
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author | Chen, Zhenyu Liu, Huaijin Zhu, Jingjing Duan, Xing Wang, Han Li, Xiangchen Zhou, Xiaolong Zhao, Ayong Yang, Songbai |
author_facet | Chen, Zhenyu Liu, Huaijin Zhu, Jingjing Duan, Xing Wang, Han Li, Xiangchen Zhou, Xiaolong Zhao, Ayong Yang, Songbai |
author_sort | Chen, Zhenyu |
collection | PubMed |
description | BACKGROUND: Promyelocytic leukemia protein (PML) is a primary component of PML nuclear bodies (PML-NBs). PML and PML-NBs play critical roles in processes like the cell cycle, DNA damage repair, apoptosis, and the antiviral immune response. Previously, we identified five porcine PML alternative splicing variants and observed an increase in the expression of these PML isoforms following Japanese encephalitis virus (JEV) infection. In this study, we examined the functional roles of these PML isoforms in JEV infection. METHODS: PML isoforms were either knocked down or overexpressed in PK15 cells, after which they were infected with JEV. Subsequently, we analyzed the gene expression of PML isoforms, JEV, and the interferon (IFN)-β signaling pathway using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Viral titers were determined through 50% tissue culture infectious dose (TCID(50)) assays. RESULTS: Our results demonstrated that the knockdown of endogenous PML promoted JEV replication, while the overexpression of PML isoforms 1, 3, 4, and 5 (PML1, PML3, PML4, and PML5) inhibited JEV replication. Further investigation revealed that PML1, PML3, PML4, and PML5 negatively regulated the expression of genes involved in the interferon (IFN)-β signaling pathway by inhibiting IFN regulatory factor 3 (IRF3) post-JEV infection. CONCLUSIONS: These findings demonstrate that porcine PML isoforms PML1, PML3, PML4, and PML5 negatively regulate IFN-β and suppress viral replication during JEV infection. The results of this study provide insight into the functional roles of porcine PML isoforms in JEV infection and the regulation of the innate immune response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-023-02212-x. |
format | Online Article Text |
id | pubmed-10687900 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-106879002023-11-30 Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells Chen, Zhenyu Liu, Huaijin Zhu, Jingjing Duan, Xing Wang, Han Li, Xiangchen Zhou, Xiaolong Zhao, Ayong Yang, Songbai Virol J Research BACKGROUND: Promyelocytic leukemia protein (PML) is a primary component of PML nuclear bodies (PML-NBs). PML and PML-NBs play critical roles in processes like the cell cycle, DNA damage repair, apoptosis, and the antiviral immune response. Previously, we identified five porcine PML alternative splicing variants and observed an increase in the expression of these PML isoforms following Japanese encephalitis virus (JEV) infection. In this study, we examined the functional roles of these PML isoforms in JEV infection. METHODS: PML isoforms were either knocked down or overexpressed in PK15 cells, after which they were infected with JEV. Subsequently, we analyzed the gene expression of PML isoforms, JEV, and the interferon (IFN)-β signaling pathway using quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blot. Viral titers were determined through 50% tissue culture infectious dose (TCID(50)) assays. RESULTS: Our results demonstrated that the knockdown of endogenous PML promoted JEV replication, while the overexpression of PML isoforms 1, 3, 4, and 5 (PML1, PML3, PML4, and PML5) inhibited JEV replication. Further investigation revealed that PML1, PML3, PML4, and PML5 negatively regulated the expression of genes involved in the interferon (IFN)-β signaling pathway by inhibiting IFN regulatory factor 3 (IRF3) post-JEV infection. CONCLUSIONS: These findings demonstrate that porcine PML isoforms PML1, PML3, PML4, and PML5 negatively regulate IFN-β and suppress viral replication during JEV infection. The results of this study provide insight into the functional roles of porcine PML isoforms in JEV infection and the regulation of the innate immune response. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s12985-023-02212-x. BioMed Central 2023-11-29 /pmc/articles/PMC10687900/ /pubmed/38031162 http://dx.doi.org/10.1186/s12985-023-02212-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Research Chen, Zhenyu Liu, Huaijin Zhu, Jingjing Duan, Xing Wang, Han Li, Xiangchen Zhou, Xiaolong Zhao, Ayong Yang, Songbai Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells |
title | Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells |
title_full | Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells |
title_fullStr | Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells |
title_full_unstemmed | Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells |
title_short | Porcine promyelocytic leukemia protein isoforms suppress Japanese encephalitis virus replication in PK15 cells |
title_sort | porcine promyelocytic leukemia protein isoforms suppress japanese encephalitis virus replication in pk15 cells |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10687900/ https://www.ncbi.nlm.nih.gov/pubmed/38031162 http://dx.doi.org/10.1186/s12985-023-02212-x |
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