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...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	HIV-1 aryl hydrocarbon receptor tryptophan metabolite transcription Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/8a679b669d9c4e35956e0aa5ecfc88e6
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spelling	oai:doaj.org-article:8a679b669d9c4e35956e0aa5ecfc88e62021-11-15T15:54:45ZTryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation10.1128/mBio.02591-192150-7511https://doaj.org/article/8a679b669d9c4e35956e0aa5ecfc88e62019-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.02591-19https://doaj.org/toc/2150-7511ABSTRACT 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.Yan-Heng ZhouLi SunJun ChenWei-Wei SunLi MaYang HanXia JinQing-Xia ZhaoTaisheng LiHongzhou LuXiu QiuJian-Hua WangAmerican Society for MicrobiologyarticleHIV-1aryl hydrocarbon receptortryptophan metabolitetranscriptionMicrobiologyQR1-502ENmBio, Vol 10, Iss 6 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	HIV-1 aryl hydrocarbon receptor tryptophan metabolite transcription Microbiology QR1-502
spellingShingle	HIV-1 aryl hydrocarbon receptor tryptophan metabolite transcription Microbiology QR1-502 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
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.
format	article
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
title	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_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_sort	tryptophan metabolism activates aryl hydrocarbon receptor-mediated pathway to promote hiv-1 infection and reactivation
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/8a679b669d9c4e35956e0aa5ecfc88e6
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Tryptophan Metabolism Activates Aryl Hydrocarbon Receptor-Mediated Pathway To Promote HIV-1 Infection and Reactivation

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