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Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types

Upon infection of its host cell, human immunodeficiency virus (HIV) establishes a quiescent and non-productive state capable of spontaneous reactivation. Diverse cell types harboring the provirus form a latent reservoir, constituting a major obstacle to curing HIV. Here, we investigate the effects o...

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Autores principales: Blanco, Alexandra, Mahajan, Tarun, Coronado, Robert A., Ma, Kelly, Demma, Dominic R., Dar, Roy D.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228244/
https://www.ncbi.nlm.nih.gov/pubmed/34201394
http://dx.doi.org/10.3390/v13061097
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author Blanco, Alexandra
Mahajan, Tarun
Coronado, Robert A.
Ma, Kelly
Demma, Dominic R.
Dar, Roy D.
author_facet Blanco, Alexandra
Mahajan, Tarun
Coronado, Robert A.
Ma, Kelly
Demma, Dominic R.
Dar, Roy D.
author_sort Blanco, Alexandra
collection PubMed
description Upon infection of its host cell, human immunodeficiency virus (HIV) establishes a quiescent and non-productive state capable of spontaneous reactivation. Diverse cell types harboring the provirus form a latent reservoir, constituting a major obstacle to curing HIV. Here, we investigate the effects of latency reversal agents (LRAs) in an HIV-infected THP-1 monocyte cell line in vitro. We demonstrate that leading drug treatments synergize activation of the HIV long terminal repeat (LTR) promoter. We establish a latency model in THP-1 monocytes using a replication incompetent HIV reporter vector with functional Tat, and show that chromatin modifiers synergize with a potent transcriptional activator to enhance HIV reactivation, similar to T-cells. Furthermore, leading reactivation cocktails are shown to differentially affect latency reactivation and surface expression of chemokine receptor type 4 (CXCR4), leading to altered host cell migration. This study investigates the effect of chromatin-modifying LRA treatments on HIV latent reactivation and cell migration in monocytes. As previously reported in T-cells, epigenetic mechanisms in monocytes contribute to controlling the relationship between latent reactivation and cell migration. Ultimately, advanced “Shock and Kill” therapy needs to successfully target and account for all host cell types represented in a complex and composite latency milieu.
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spelling pubmed-82282442021-06-26 Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types Blanco, Alexandra Mahajan, Tarun Coronado, Robert A. Ma, Kelly Demma, Dominic R. Dar, Roy D. Viruses Article Upon infection of its host cell, human immunodeficiency virus (HIV) establishes a quiescent and non-productive state capable of spontaneous reactivation. Diverse cell types harboring the provirus form a latent reservoir, constituting a major obstacle to curing HIV. Here, we investigate the effects of latency reversal agents (LRAs) in an HIV-infected THP-1 monocyte cell line in vitro. We demonstrate that leading drug treatments synergize activation of the HIV long terminal repeat (LTR) promoter. We establish a latency model in THP-1 monocytes using a replication incompetent HIV reporter vector with functional Tat, and show that chromatin modifiers synergize with a potent transcriptional activator to enhance HIV reactivation, similar to T-cells. Furthermore, leading reactivation cocktails are shown to differentially affect latency reactivation and surface expression of chemokine receptor type 4 (CXCR4), leading to altered host cell migration. This study investigates the effect of chromatin-modifying LRA treatments on HIV latent reactivation and cell migration in monocytes. As previously reported in T-cells, epigenetic mechanisms in monocytes contribute to controlling the relationship between latent reactivation and cell migration. Ultimately, advanced “Shock and Kill” therapy needs to successfully target and account for all host cell types represented in a complex and composite latency milieu. MDPI 2021-06-08 /pmc/articles/PMC8228244/ /pubmed/34201394 http://dx.doi.org/10.3390/v13061097 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Blanco, Alexandra
Mahajan, Tarun
Coronado, Robert A.
Ma, Kelly
Demma, Dominic R.
Dar, Roy D.
Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types
title Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types
title_full Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types
title_fullStr Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types
title_full_unstemmed Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types
title_short Synergistic Chromatin-Modifying Treatments Reactivate Latent HIV and Decrease Migration of Multiple Host-Cell Types
title_sort synergistic chromatin-modifying treatments reactivate latent hiv and decrease migration of multiple host-cell types
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8228244/
https://www.ncbi.nlm.nih.gov/pubmed/34201394
http://dx.doi.org/10.3390/v13061097
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