Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription

Jing Wen; Caiqi Zhao; Jie Chen; Shuting Song; Zhekai Lin; Shitao Xie; Huaxin Qi; Jianhua Wang; Xiao Su

Cell Insight (Jun 2022)

Activation of α7 nicotinic acetylcholine receptor promotes HIV-1 transcription

Jing Wen,
Caiqi Zhao,
Jie Chen,
Shuting Song,
Zhekai Lin,
Shitao Xie,
Huaxin Qi,
Jianhua Wang,
Xiao Su

Affiliations

Jing Wen: Unit 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
Caiqi Zhao: Unit 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
Jie Chen: Unit 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
Shuting Song: Unit 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
Zhekai Lin: Unit 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
Shitao Xie: Unit 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
Huaxin Qi: Unit 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
Jianhua Wang: Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, 510670, China
Xiao Su: Unit 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.

Journal volume & issue: Vol. 1, no. 3
p. 100028

Abstract

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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.

Published in Cell Insight

ISSN: 2772-8927 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General); Medicine: Medicine (General)
Website: https://www.sciencedirect.com/journal/cell-insight

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