Journal article
Broad activation of latent HIV-1 in vivo
K Barton, B Hiener, A Winckelmann, TA Rasmussen, W Shao, K Byth, R Lanfear, A Solomon, J McMahon, S Harrington, M Buzon, M Lichterfeld, PW Denton, R Olesen, L Østergaard, M Tolstrup, SR Lewin, OS Søgaard, S Palmer
Nature Communications | NATURE PORTFOLIO | Published : 2016
DOI: 10.1038/ncomms12731
Abstract
The shock and kill approach to cure human immunodeficiency virus (HIV) includes transcriptional induction of latent HIV-1 proviruses using latency-reversing agents (LRAs) with targeted immunotherapy to purge infected cells. The administration of LRAs (panobinostat or vorinostat) to HIV-1-infected individuals on antiretroviral therapy induces a significant increase in cell-associated unspliced (CA-US) HIV-1 RNA from CD4 + T cells. However, it is important to discern whether the increases in CA-US HIV-1 RNA are due to limited or broad activation of HIV-1 proviruses. Here we use single-genome sequencing to find that the RNA transcripts observed following LRA administration are genetically diver..
View full abstractGrants
Awarded by National Institutes of Health
Funding Acknowledgements
This work was supported by the Delaney AIDS Research Enterprise (DARE) to Find a Cure 1U19AI096109, the National Institutes of Health grant 1R21AI113096 (S.P., S.R.L. and T.A.R.), amfAR grant 108830 with support from FAIR: the Foundation for AIDS and Immune Research, the amfAR Research Consortium on HIV Eradication (108928-56-RGRL) and the National Health and Medical Research Council (NHMRC) of Australia (grant APP1061681). S.R.L. is supported by a practitioner fellowship and J.M. by an early career fellowship from the NHMRC of Australia. T.A.R., L.O., M.T., O.S.S. and S.R.L. were supported by a grant from the Danish Council for Strategic Research (grant #0603-00521B). We thank Dr Timothy Schlub for statistics consultation. We acknowledge the participation and commitment of study participants, which made the study possible.