Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection
Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transc...
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MDPI AG
2023-07-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/15/8/1646 |
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| author | Zhiyan Zhao Jing Li Ye Feng Xiaoping Kang Yuchang Li Yuehong Chen Wei Li Wenguang Yang Lu Zhao Shenghai Huang Sen Zhang Tao Jiang |
| author_facet | Zhiyan Zhao Jing Li Ye Feng Xiaoping Kang Yuchang Li Yuehong Chen Wei Li Wenguang Yang Lu Zhao Shenghai Huang Sen Zhang Tao Jiang |
| author_sort | Zhiyan Zhao |
| collection | DOAJ |
| description | Influenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus–host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2′-5′-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense. |
| first_indexed | 2024-03-10T23:30:51Z |
| format | Article |
| id | doaj.art-982242a0561140bd906194776c4fcb7f |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T23:30:51Z |
| publishDate | 2023-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-982242a0561140bd906194776c4fcb7f2023-11-19T03:19:39ZengMDPI AGViruses1999-49152023-07-01158164610.3390/v15081646Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus InfectionZhiyan Zhao0Jing Li1Ye Feng2Xiaoping Kang3Yuchang Li4Yuehong Chen5Wei Li6Wenguang Yang7Lu Zhao8Shenghai Huang9Sen Zhang10Tao Jiang11School of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaState Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Academy of Military Medical Sciences, Beijing 100071, ChinaSchool of Basic Medical Sciences, Anhui Medical University, Hefei 230032, ChinaInfluenza A virus (IAV) is a leading cause of human respiratory infections and poses a major public health concern. IAV replication can affect the expression of DNA methyltransferases (DNMTs), and the subsequent changes in DNA methylation regulate gene expression and may lead to abnormal gene transcription and translation, yet the underlying mechanisms of virus-induced epigenetic changes from DNA methylation and its role in virus–host interactions remain elusive. Here in this paper, we showed that DNMT1 expression could be suppressed following the inhibition of miR-142-5p or the PI3K/AKT signaling pathway during IAV infection, resulting in demethylation of the promotor region of the 2′-5′-oligoadenylate synthetase-like (OASL) protein and promotion of its expression in A549 cells. OASL expression enhanced RIG-I-mediated interferon induction and then suppressed replication of IAV. Our study elucidated an innate immunity mechanism by which up-regulation of OASL contributes to host antiviral responses via epigenetic modifications in IAV infection, which could provide important insights into the understanding of viral pathogenesis and host antiviral defense.https://www.mdpi.com/1999-4915/15/8/1646influenza A virusDNA methyltransferase 1miR-142-5pPI3K/AKT2′-5′-oligoadenylate synthetase-like protein |
| spellingShingle | Zhiyan Zhao Jing Li Ye Feng Xiaoping Kang Yuchang Li Yuehong Chen Wei Li Wenguang Yang Lu Zhao Shenghai Huang Sen Zhang Tao Jiang Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection Viruses influenza A virus DNA methyltransferase 1 miR-142-5p PI3K/AKT 2′-5′-oligoadenylate synthetase-like protein |
| title | Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection |
| title_full | Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection |
| title_fullStr | Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection |
| title_full_unstemmed | Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection |
| title_short | Host DNA Demethylation Induced by DNMT1 Inhibition Up-Regulates Antiviral OASL Protein during Influenza a Virus Infection |
| title_sort | host dna demethylation induced by dnmt1 inhibition up regulates antiviral oasl protein during influenza a virus infection |
| topic | influenza A virus DNA methyltransferase 1 miR-142-5p PI3K/AKT 2′-5′-oligoadenylate synthetase-like protein |
| url | https://www.mdpi.com/1999-4915/15/8/1646 |
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