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OGG1 inhibition suppresses African swine fever virus replication
African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Wuhan Institute of Virology, Chinese Academy of Sciences
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006199/ https://www.ncbi.nlm.nih.gov/pubmed/36435451 http://dx.doi.org/10.1016/j.virs.2022.11.006 |
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author | Fan, Jie Lv, Xinqian Yang, Saixia Geng, Shuxian Yang, Jifei Zhao, Yaru Zhang, Zhonghui Liu, Zhijie Guan, Guiquan Luo, Jianxun Zeng, Qiaoying Yin, Hong Niu, Qingli |
author_facet | Fan, Jie Lv, Xinqian Yang, Saixia Geng, Shuxian Yang, Jifei Zhao, Yaru Zhang, Zhonghui Liu, Zhijie Guan, Guiquan Luo, Jianxun Zeng, Qiaoying Yin, Hong Niu, Qingli |
author_sort | Fan, Jie |
collection | PubMed |
description | African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), has been linked to the pathogenesis of different diseases associated with viral infections. However, the role of OGG1-base excision repair (BER) in ASFV infection has been poorly investigated. Our study aimed to characterize the alteration of host reactive oxygen species (ROS) and OGG1 and to analyse the role of OGG1 in ASFV infection. We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1. Viral yield, transcription level, and protein synthesis were reduced in ASFV-infected primary alveolar macrophages (PAMs) treated by TH5487 or SU0268 inhibiting OGG1. The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs. Furthermore, OGG1 was found to negatively regulate interferon β (IFN-β) production during ASFV infection and IFN-β could be activated by OGG1 inhibition with TH5487 and SU0268, which blocked OGG1 binding to 8-oxoG. Additionally, the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-β production to further affect ASFV replication. These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection. |
format | Online Article Text |
id | pubmed-10006199 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Wuhan Institute of Virology, Chinese Academy of Sciences |
record_format | MEDLINE/PubMed |
spelling | pubmed-100061992023-03-12 OGG1 inhibition suppresses African swine fever virus replication Fan, Jie Lv, Xinqian Yang, Saixia Geng, Shuxian Yang, Jifei Zhao, Yaru Zhang, Zhonghui Liu, Zhijie Guan, Guiquan Luo, Jianxun Zeng, Qiaoying Yin, Hong Niu, Qingli Virol Sin Research Article African swine fever virus (ASFV) is an important pathogen that causes a highly contagious and lethal disease in swine, for which neither a vaccine nor treatment is available. The DNA repair enzyme 8-oxoguanine DNA glycosylase 1 (OGG1), which excises the oxidative base lesion 8-oxo-7,8-dihydroguanine (8-oxoG), has been linked to the pathogenesis of different diseases associated with viral infections. However, the role of OGG1-base excision repair (BER) in ASFV infection has been poorly investigated. Our study aimed to characterize the alteration of host reactive oxygen species (ROS) and OGG1 and to analyse the role of OGG1 in ASFV infection. We found that ASFV infection induced high levels and dynamic changes in ROS and 8-oxoG and consistently increased the expression of OGG1. Viral yield, transcription level, and protein synthesis were reduced in ASFV-infected primary alveolar macrophages (PAMs) treated by TH5487 or SU0268 inhibiting OGG1. The expression of BER pathway associated proteins of ASFV was also suppressed in OGG1-inhibited PAMs. Furthermore, OGG1 was found to negatively regulate interferon β (IFN-β) production during ASFV infection and IFN-β could be activated by OGG1 inhibition with TH5487 and SU0268, which blocked OGG1 binding to 8-oxoG. Additionally, the interaction of OGG1 with viral MGF360-14-L protein could disturb IFN-β production to further affect ASFV replication. These results suggest that OGG1 plays the crucial role in successful viral infection and OGG1 inhibitors SU0268 or TH5487 could be used as antiviral agents for ASFV infection. Wuhan Institute of Virology, Chinese Academy of Sciences 2022-11-23 /pmc/articles/PMC10006199/ /pubmed/36435451 http://dx.doi.org/10.1016/j.virs.2022.11.006 Text en © 2022 The Authors https://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 | Research Article Fan, Jie Lv, Xinqian Yang, Saixia Geng, Shuxian Yang, Jifei Zhao, Yaru Zhang, Zhonghui Liu, Zhijie Guan, Guiquan Luo, Jianxun Zeng, Qiaoying Yin, Hong Niu, Qingli OGG1 inhibition suppresses African swine fever virus replication |
title | OGG1 inhibition suppresses African swine fever virus replication |
title_full | OGG1 inhibition suppresses African swine fever virus replication |
title_fullStr | OGG1 inhibition suppresses African swine fever virus replication |
title_full_unstemmed | OGG1 inhibition suppresses African swine fever virus replication |
title_short | OGG1 inhibition suppresses African swine fever virus replication |
title_sort | ogg1 inhibition suppresses african swine fever virus replication |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006199/ https://www.ncbi.nlm.nih.gov/pubmed/36435451 http://dx.doi.org/10.1016/j.virs.2022.11.006 |
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