Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors

The presence of replication-competent HIV-1 –which resides mainly in resting CD4+ T cells–is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoi...

Full description

Bibliographic Details
Main Authors:	Perdigão, Pedro, Gaj, Thomas, Santa-Marta, Mariana, Barbas, Carlos F., Goncalves, Joao
Format:	Online
Language:	English
Published:	Public Library of Science 2016
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774903/

id	pubmed-4774903
recordtype	oai_dc
spelling	pubmed-47749032016-03-10 Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors Perdigão, Pedro Gaj, Thomas Santa-Marta, Mariana Barbas, Carlos F. Goncalves, Joao Research Article The presence of replication-competent HIV-1 –which resides mainly in resting CD4+ T cells–is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection. Public Library of Science 2016-03-02 /pmc/articles/PMC4774903/ /pubmed/26933881 http://dx.doi.org/10.1371/journal.pone.0150037 Text en © 2016 Perdigão et al http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Perdigão, Pedro Gaj, Thomas Santa-Marta, Mariana Barbas, Carlos F. Goncalves, Joao
spellingShingle	Perdigão, Pedro Gaj, Thomas Santa-Marta, Mariana Barbas, Carlos F. Goncalves, Joao Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
author_facet	Perdigão, Pedro Gaj, Thomas Santa-Marta, Mariana Barbas, Carlos F. Goncalves, Joao
author_sort	Perdigão, Pedro
title	Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
title_short	Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
title_full	Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
title_fullStr	Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
title_full_unstemmed	Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors
title_sort	reactivation of latent hiv-1 expression by engineered tale transcription factors
description	The presence of replication-competent HIV-1 –which resides mainly in resting CD4+ T cells–is a major hurdle to its eradication. While pharmacological approaches have been useful for inducing the expression of this latent population of virus, they have been unable to purge HIV-1 from all its reservoirs. Additionally, many of these strategies have been associated with adverse effects, underscoring the need for alternative approaches capable of reactivating viral expression. Here we show that engineered transcriptional modulators based on customizable transcription activator-like effector (TALE) proteins can induce gene expression from the HIV-1 long terminal repeat promoter, and that combinations of TALE transcription factors can synergistically reactivate latent viral expression in cell line models of HIV-1 latency. We further show that complementing TALE transcription factors with Vorinostat, a histone deacetylase inhibitor, enhances HIV-1 expression in latency models. Collectively, these findings demonstrate that TALE transcription factors are a potentially effective alternative to current pharmacological routes for reactivating latent virus and that combining synthetic transcriptional activators with histone deacetylase inhibitors could lead to the development of improved therapies for latent HIV-1 infection.
publisher	Public Library of Science
publishDate	2016
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4774903/
_version_	1613546306740944896

Reactivation of Latent HIV-1 Expression by Engineered TALE Transcription Factors

Similar Items