Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription
Alpha7 nicotinic acetylcholine receptor (α7 nAChR), a hub of the cholinergic anti-inflammatory pathway (CAP), is required for the treatment of inflammatory diseases. HIV-1 infection can upregulate the expression of α7 nAChR in T lymphocytes and affect the role of CAP. However, whether α7 nAChR regul...
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| Format: | Article |
| Language: | English |
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Elsevier
2022-06-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892722000256 |
| _version_ | 1818472987035172864 |
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| author | Jing Wen Caiqi Zhao Jie Chen Shuting Song Zhekai Lin Shitao Xie Huaxin Qi Jianhua Wang Xiao Su |
| author_facet | Jing Wen Caiqi Zhao Jie Chen Shuting Song Zhekai Lin Shitao Xie Huaxin Qi Jianhua Wang Xiao Su |
| author_sort | Jing Wen |
| collection | DOAJ |
| description | Alpha7 nicotinic acetylcholine receptor (α7 nAChR), a hub of the cholinergic anti-inflammatory pathway (CAP), is required for the treatment of inflammatory diseases. HIV-1 infection can upregulate the expression of α7 nAChR in T lymphocytes and affect the role of CAP. However, whether α7 nAChR regulates HIV-1 infection in CD4+ T cells is unclear. In this study, we first found that activation of α7 nAChR by GTS-21 (an α7 nAChR agonist) can promote the transcription of HIV-1 proviral DNA. Then, through transcriptome sequencing analysis, we found that p38 MAPK signaling was enriched in GTS-21 treated HIV-latent T cells. Mechanistically, activation of α7 nAChR could increase reactive oxygen species (ROS), reduce DUSP1 and DUSP6, and consequently enhance the phosphorylation of p38 MAPK. By co-immunoprecipitation and liquid chromatography tandem mass spectrometry, we found that p-p38 MAPK interacted with Lamin B1 (LMNB1). Activation of α7 nAChR increased the binding between p-p38 MAPK and LMNB1. We confirmed that knockdown of MAPK14 significantly downregulated NFATC4, a key activator of HIV-1 transcription. Taken together, activation of the α7 nAChR could trigger ROS/p-p38 MAPK/LMNB1/NFATC4 signaling pathway enhancing HIV-1 transcription. We have revealed an unrecognized mechanism of α7 nAChR-mediated neuroimmune regulation of HIV infection. |
| first_indexed | 2024-04-14T04:15:30Z |
| format | Article |
| id | doaj.art-a1fde6c3dd9d48e5a6a7555bbd7421bf |
| institution | Directory Open Access Journal |
| issn | 2772-8927 |
| language | English |
| last_indexed | 2024-04-14T04:15:30Z |
| publishDate | 2022-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Insight |
| spelling | doaj.art-a1fde6c3dd9d48e5a6a7555bbd7421bf2022-12-22T02:12:51ZengElsevierCell Insight2772-89272022-06-0113100028Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcriptionJing Wen0Caiqi Zhao1Jie Chen2Shuting Song3Zhekai Lin4Shitao Xie5Huaxin Qi6Jianhua Wang7Xiao Su8Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, ChinaGuangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510670, ChinaUnit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; CAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China; University of Chinese Academy of Sciences, Beijing, 100049, China; Corresponding author. PhD. Unit of Respiratory Infection and Immunity, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, 200031, China.Alpha7 nicotinic acetylcholine receptor (α7 nAChR), a hub of the cholinergic anti-inflammatory pathway (CAP), is required for the treatment of inflammatory diseases. HIV-1 infection can upregulate the expression of α7 nAChR in T lymphocytes and affect the role of CAP. However, whether α7 nAChR regulates HIV-1 infection in CD4+ T cells is unclear. In this study, we first found that activation of α7 nAChR by GTS-21 (an α7 nAChR agonist) can promote the transcription of HIV-1 proviral DNA. Then, through transcriptome sequencing analysis, we found that p38 MAPK signaling was enriched in GTS-21 treated HIV-latent T cells. Mechanistically, activation of α7 nAChR could increase reactive oxygen species (ROS), reduce DUSP1 and DUSP6, and consequently enhance the phosphorylation of p38 MAPK. By co-immunoprecipitation and liquid chromatography tandem mass spectrometry, we found that p-p38 MAPK interacted with Lamin B1 (LMNB1). Activation of α7 nAChR increased the binding between p-p38 MAPK and LMNB1. We confirmed that knockdown of MAPK14 significantly downregulated NFATC4, a key activator of HIV-1 transcription. Taken together, activation of the α7 nAChR could trigger ROS/p-p38 MAPK/LMNB1/NFATC4 signaling pathway enhancing HIV-1 transcription. We have revealed an unrecognized mechanism of α7 nAChR-mediated neuroimmune regulation of HIV infection.http://www.sciencedirect.com/science/article/pii/S2772892722000256HIV-1α7 nAChRROSp38 MAPKLMNB1 |
| spellingShingle | Jing Wen Caiqi Zhao Jie Chen Shuting Song Zhekai Lin Shitao Xie Huaxin Qi Jianhua Wang Xiao Su Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription Cell Insight HIV-1 α7 nAChR ROS p38 MAPK LMNB1 |
| title | Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription |
| title_full | Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription |
| title_fullStr | Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription |
| title_full_unstemmed | Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription |
| title_short | Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription |
| title_sort | activation of α7 nicotinic acetylcholine receptor promotes hiv 1 transcription |
| topic | HIV-1 α7 nAChR ROS p38 MAPK LMNB1 |
| url | http://www.sciencedirect.com/science/article/pii/S2772892722000256 |
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