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

Authors :
Alexandra Blanco
Tarun Mahajan
Robert A. Coronado
Kelly Ma
Dominic R. Demma
Roy D. Dar
Source :
Viruses, Vol 13, Iss 6, p 1097 (2021)
Publication Year :
2021
Publisher :
MDPI AG, 2021.

Abstract

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.

Details

Language :
English
ISSN :
13061097 and 19994915
Volume :
13
Issue :
6
Database :
Directory of Open Access Journals
Journal :
Viruses
Publication Type :
Academic Journal
Accession number :
edsdoj.3dfffe37cf134212a74b4c9075379df3
Document Type :
article
Full Text :
https://doi.org/10.3390/v13061097