Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1.

AIDS
Christina C ChangSharon R Lewin

Abstract

To determine whether variation in cell-associated unspliced (CA-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 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. Th...Continue Reading

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Citations

Oct 20, 2018·Nature Immunology·Fu Sheng WangSharon R Lewin
Aug 9, 2020·Scientific Reports·Helene BorrmannXiaodong Zhuang
Nov 10, 2020·Journal of Biological Rhythms·Helene BorrmannXiaodong Zhuang
Mar 14, 2021·Nature Communications·Xiaodong ZhuangJane A McKeating
Oct 17, 2021·The Journal of Infectious Diseases·Jared SternSharon R Lewin
Jan 29, 2019·Antiviral Research·Christian BrechotScott Weaver

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