期刊
MBIO
卷 10, 期 6, 页码 -出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/mBio.02591-19
关键词
HIV-1; aryl hydrocarbon receptor; tryptophan metabolite; transcription
类别
资金
- National Grant Program on Key Infectious Disease [2018ZX10301101-003-002]
- Chinese Academy of Sciences [QYZDB-SSW-SMC059]
- Natural Science Foundation of China (NSFC) [81572001, 81873965]
- NSFC [81601802]
- China Postdoctoral Science Foundation [2017M611624]
- Guangzhou Women and Children's Medical Center
- Young Talent fund of University Association for Science and Technology in Shaanxi, China [20170207]
- National Megaproject on Key Infectious Disease [2017ZX10202102-004-003]
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.
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