Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation
ABSTRACT Multiple cellular metabolic pathways are altered by HIV-1 infection, with an impact on immune activation, inflammation, and acquisition of non-AIDS comorbid diseases. The dysfunction of tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenes...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2019-12-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.02591-19 |
| _version_ | 1818856707223191552 |
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| author | Yan-Heng Zhou Li Sun Jun Chen Wei-Wei Sun Li Ma Yang Han Xia Jin Qing-Xia Zhao Taisheng Li Hongzhou Lu Xiu Qiu Jian-Hua Wang |
| author_facet | Yan-Heng Zhou Li Sun Jun Chen Wei-Wei Sun Li Ma Yang Han Xia Jin Qing-Xia Zhao Taisheng Li Hongzhou Lu Xiu Qiu Jian-Hua Wang |
| author_sort | Yan-Heng Zhou |
| collection | DOAJ |
| description | ABSTRACT Multiple cellular metabolic pathways are altered by HIV-1 infection, with an impact on immune activation, inflammation, and acquisition of non-AIDS comorbid diseases. The dysfunction of tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the underlying mechanism remains unknown. In this study, we demonstrated that the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is activated by Trp metabolites to promote HIV-1 infection and reactivation. AHR directly binds to the HIV-1 5′ long terminal repeat (5′-LTR) at the molecular level to activate viral transcription and infection, and AHR activation by Trp metabolites increases its nuclear translocation and association with the HIV 5′-LTR; moreover, the binding of AHR with HIV-1 Tat facilitates the recruitment of positive transcription factors to viral promoters. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection. IMPORTANCE Cellular metabolic pathways that are altered by HIV-1 infection may accelerate disease progression. Dysfunction in tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the mechanism responsible was not known. This study demonstrates that Trp metabolites augment the activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, to promote HIV-1 infection and transcription. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection. |
| first_indexed | 2024-12-19T08:28:46Z |
| format | Article |
| id | doaj.art-8a679b669d9c4e35956e0aa5ecfc88e6 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T08:28:46Z |
| publishDate | 2019-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-8a679b669d9c4e35956e0aa5ecfc88e62022-12-21T20:29:15ZengAmerican Society for MicrobiologymBio2150-75112019-12-0110610.1128/mBio.02591-19Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and ReactivationYan-Heng Zhou0Li Sun1Jun Chen2Wei-Wei Sun3Li Ma4Yang Han5Xia Jin6Qing-Xia Zhao7Taisheng Li8Hongzhou Lu9Xiu Qiu10Jian-Hua Wang11The Joint Center for Infection and Immunity between Guangzhou Institute of Pediatrics, Guangzhou Women and Childrenˋs Medical Center, Guangzhou, China, and Institut Pasteur of Shanghai, Chinese Academy of Sciences (CAS), Shanghai, ChinaCAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Infections and Immunity, Shanghai Public Health Clinical Center, Shanghai, ChinaCAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaCAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, ChinaCAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaDepartment of Infection, Zhengzhou Sixth People’s Hospital, Zhengzhou, ChinaDepartment of Infectious Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, ChinaDepartment of Infections and Immunity, Shanghai Public Health Clinical Center, Shanghai, ChinaThe Joint Center for Infection and Immunity between Guangzhou Institute of Pediatrics, Guangzhou Women and Childrenˋs Medical Center, Guangzhou, China, and Institut Pasteur of Shanghai, Chinese Academy of Sciences (CAS), Shanghai, ChinaCAS Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Chinese Academy of Sciences, Shanghai, ChinaABSTRACT Multiple cellular metabolic pathways are altered by HIV-1 infection, with an impact on immune activation, inflammation, and acquisition of non-AIDS comorbid diseases. The dysfunction of tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the underlying mechanism remains unknown. In this study, we demonstrated that the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, is activated by Trp metabolites to promote HIV-1 infection and reactivation. AHR directly binds to the HIV-1 5′ long terminal repeat (5′-LTR) at the molecular level to activate viral transcription and infection, and AHR activation by Trp metabolites increases its nuclear translocation and association with the HIV 5′-LTR; moreover, the binding of AHR with HIV-1 Tat facilitates the recruitment of positive transcription factors to viral promoters. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection. IMPORTANCE Cellular metabolic pathways that are altered by HIV-1 infection may accelerate disease progression. Dysfunction in tryptophan (Trp) metabolism has been observed clinically in association with accelerated HIV-1 pathogenesis, but the mechanism responsible was not known. This study demonstrates that Trp metabolites augment the activation of aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, to promote HIV-1 infection and transcription. These findings not only elucidate a previously unappreciated mechanism through which cellular Trp metabolites affect HIV pathogenesis but also suggest that a downstream target AHR may be a potential target for modulating HIV-1 infection.https://journals.asm.org/doi/10.1128/mBio.02591-19HIV-1aryl hydrocarbon receptortryptophan metabolitetranscription |
| spellingShingle | Yan-Heng Zhou Li Sun Jun Chen Wei-Wei Sun Li Ma Yang Han Xia Jin Qing-Xia Zhao Taisheng Li Hongzhou Lu Xiu Qiu Jian-Hua Wang Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation mBio HIV-1 aryl hydrocarbon receptor tryptophan metabolite transcription |
| title | Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation |
| title_full | Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation |
| title_fullStr | Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation |
| title_full_unstemmed | Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation |
| title_short | Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation |
| title_sort | tryptophan metabolism activates aryl hydrocarbon receptor mediated pathway to promote hiv 1 infection and reactivation |
| topic | HIV-1 aryl hydrocarbon receptor tryptophan metabolite transcription |
| url | https://journals.asm.org/doi/10.1128/mBio.02591-19 |
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