期刊
AIDS
卷 32, 期 15, 页码 2119-2128出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/QAD.0000000000001937
关键词
brain-and-muscle-ARNT-like-1; circadian rhythm; HIV; HIV latency; HIV transcription; stress; unspliced RNA
资金
- National Institutes of Health (NIH) Delaney AIDS Research Enterprise [DARE U19 AI096109, UM1 AI126611-01]
- NIH [R01-AI028433, R01-OD011095]
- American Foundation for AIDS Research (amFAR) Research consortium on HIV eradication (ARCHE)
- National Health and Medical Research Council (NHMRC) of Australia
Objective(s): To determine whether variation in cell-associated unspliced (CA-US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis. Methods: Prospective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the circadianlocomotor- output-cycles-kaput (CLOCK)-associated genes quantified by real time PCR. CLOCK-associated proteins were over-expressed in a cell line stably transfected with an HIV long-terminal repeat (LTR) luciferase reporter. Results: Using a mixed effects model, there was a significant increase in log-CA-US RNA at the third visit compared with the first visit (effect size of 0.619 with standard error (SE) of 0.098, P < 0.001) and an independent effect of time of blood draw (effect size 0.051 (SE 0.025), P = 0.040). The CLOCK-associated gene, brain-and-muscle-ARNT-like-1 (BMAL-1) had a significant relationship with log CA-US HIV RNA (effect size 8.508 (SE 3.777), P = 0.028) and also with time (P = 0.045). Over expression of BMAL-1 and CLOCK in a cell line stably transfected with an HIV-LTR luciferase reporter resulted in an increase in luciferase expression and this was reduced following mutation of the second E-box in the HIV-LTR. Conclusion: The basal level of HIV transcription on ART can vary significantly and is modulated by the circadian regulator BMAL-1, amongst other factors. Copyright (C) 2018 Wolters Kluwer Health, Inc. All rights reserved.
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