Title |
Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1
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Published in |
AIDS, September 2018
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DOI | 10.1097/qad.0000000000001937 |
Pubmed ID | |
Authors |
Christina C Chang, Vivek Naranbhai, Jared Stern, Michael Roche, Ashanti Dantanarayana, Ruian Ke, Surekha Tennakoon, Ajantha Solomon, Rebecca Hoh, Wendy Hartogensis, Frederick M Hecht, Ken Sikaris, David J Price, Julian H Elliott, Steven G Deeks, Melissa Churchill, Paul U Cameron, Nicolas Hengartner, Alan S Perelson, Sharon R Lewin |
Abstract |
To determine whether variation in cell associated (CA) unspliced (US) HIV RNA in HIV-infected individuals on antiretroviral therapy (ART) has a circadian basis. Prospective observational study of HIV-infected individuals on ART. Blood was collected on three occasions and CA-US HIV RNA and mRNA of the Circadian-locomotor-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. Using a mixed effects model, there was a significant increase in log-CA-US RNA at the third visit compared to 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. The basal level of HIV transcription on ART can vary significantly and is modulated by the circadian regulator BMAL-1, amongst other factors. |
X Demographics
Geographical breakdown
Country | Count | As % |
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United States | 1 | 50% |
Unknown | 1 | 50% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 2 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 43 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 6 | 14% |
Other | 4 | 9% |
Student > Master | 3 | 7% |
Researcher | 3 | 7% |
Student > Bachelor | 3 | 7% |
Other | 6 | 14% |
Unknown | 18 | 42% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 10 | 23% |
Immunology and Microbiology | 4 | 9% |
Biochemistry, Genetics and Molecular Biology | 3 | 7% |
Business, Management and Accounting | 2 | 5% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
Other | 4 | 9% |
Unknown | 19 | 44% |