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

Chang, C, Naranbhai, V, Stern, J, Roche, M and Churchill, M., et al., 2018, 'Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1', AIDS, vol. 32, no. 15, pp. 2119-2128.


Document type: Journal Article
Collection: Journal Articles

Title Variation in cell-associated unspliced HIV RNA on antiretroviral therapy is associated with the circadian regulator brain-and-muscle-ARNT-like-1
Author(s) Chang, C
Naranbhai, V
Stern, J
Roche, M
Churchill, M., et al.,
Year 2018
Journal name AIDS
Volume number 32
Issue number 15
Start page 2119
End page 2128
Total pages 10
Publisher Lippincott Williams & Wilkins
Abstract 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 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. 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.
Subject Medical Virology
Keyword(s) brain-and-muscle-ARNT-like-1
circadian rhythm
HIV
HIV latency
HIV transcription
stress
unspliced RNA
DOI - identifier 10.1097/QAD.0000000000001937
Copyright notice © 2018 Wolters Kluwer Health
ISSN 0269-9370
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 4 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 0 times in Scopus Article
Altmetric details:
Access Statistics: 7 Abstract Views  -  Detailed Statistics
Created: Mon, 29 Apr 2019, 13:04:00 EST by Catalyst Administrator
© 2014 RMIT Research Repository • Powered by Fez SoftwareContact us