Curaxin CBL0100 Blocks HIV-1 Replication and Reactivation through Inhibition of Viral Transcriptional Elongation

Frontiers in Microbiology
Maxime JeanJian Zhu

Abstract

Despite combination antiretroviral therapy (cART), acquired immunodeficiency syndrome (AIDS), predominantly caused by the human immunodeficiency virus type 1 (HIV-1), remains incurable. The barrier to a cure lies in the virus' ability to establish a latent infection in HIV/AIDS patients. Unsurprisingly, efforts for a sterilizing cure have focused on the "shock and kill" strategy using latency-reversing agents (LRAs) to complement cART in order to eliminate these latent reservoirs. However, this method faces numerous challenges. Recently, the "block and lock" strategy has been proposed. It aims to reinforce a deep state of latency and prevent sporadic reactivation ("blip") of HIV-1 using latency-promoting agents (LPAs) for a functional cure. Our studies of curaxin 100 (CBL0100), a small-molecule targeting the facilitates chromatin transcription (FACT) complex, show that it blocks both HIV-1 replication and reactivation in in vitro and ex vivo models of HIV-1. Mechanistic investigation elucidated that CBL0100 preferentially targets HIV-1 transcriptional elongation and decreases the occupancy of RNA Polymerase II (Pol II) and FACT at the HIV-1 promoter region. In conclusion, CBL0100 is a newly identified inhibitor of HIV-1 transcr...Continue Reading

References

Jun 29, 1999·Cold Spring Harbor Symposia on Quantitative Biology·M E GarberK A Jones
Jun 16, 2004·Current Opinion in Genetics & Development·Rimma Belotserkovskaya, Danny Reinberg
Dec 21, 2006·Nature Reviews. Neuroscience·Ronald EllisEliezer Masliah
Oct 14, 2008·Blood·Alberto Bosque, Vicente Planelles
Jan 28, 2009·BMJ : British Medical Journal·Steven G Deeks, Andrew N Phillips
Jun 23, 2009·Nature Medicine·Nicolas ChomontRafick-Pierre Sékaly
Feb 3, 2011·Virology·Matthew J PaceUna O'Doherty
Aug 13, 2011·Science Translational Medicine·Alexander V GasparianKaterina V Gurova
Oct 21, 2011·Journal of Virology·Paul W DentonJ Victor Garcia
Nov 22, 2011·Cell Host & Microbe·Melanie OttQiang Zhou
Oct 9, 2012·Cell Reports·Jian ZhuAbraham L Brass
Jul 13, 2013·Cell Death & Disease·A D BadleyS R Lewin
Nov 19, 2013·Cell·Debbie S Ruelas, Warner C Greene
Apr 25, 2014·Viruses·Amit KumarGeorges Herbein
Nov 18, 2014·Nature Reviews. Microbiology·Nancie M ArchinDavid M Margolis
Mar 31, 2015·The Journal of Clinical Investigation·Gregory M LairdRobert F Siliciano
Dec 16, 2016·Cell Host & Microbe·Emilie BesnardEric Verdin
Jan 12, 2017·Trends in Immunology·Gilles DarcisCarine Van Lint

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Citations

Nov 6, 2018·PLoS Pathogens·Marie LeozKoh Fujinaga
Apr 17, 2019·Journal of Medical Virology·Maxime J JeanJian Zhu
May 22, 2020·Drugs·Lucia Bailon AlvarezChristian Brander
Jan 16, 2020·Viruses·Gerlinde VansantZeger Debyser
Apr 12, 2020·Viruses·Hongping JinDavid Harrich
Jul 31, 2018·AIDS Research and Human Retroviruses·Sergio Castro-GonzalezRuth Serra-Moreno
Apr 4, 2019·Retrovirology·Gerlinde VansantZeger Debyser
Jun 12, 2018·Frontiers in Microbiology·Mie Kobayashi-IshiharaYasuko Tsunetsugu-Yokota
Dec 19, 2020·Viruses·Ines Moranguinho, Susana T Valente

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Methods Mentioned

BETA
transfection
leukapheresis
ELISA
PCR
flow cytometry
ChIP-PCR
immunoprecipitations
immunoprecipitation
ChIP

Software Mentioned

GraphPad Prism

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