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Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation
Human Immunodeficiency Virus-1 (HIV) remains a global health challenge due to the latent HIV reservoirs in people living with HIV (PLWH). Dormant yet replication competent HIV harbored in the resting CD4+ T cells cannot be purged by antiretroviral therapy (ART) alone. One approach of HIV cure is the...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960990/ https://www.ncbi.nlm.nih.gov/pubmed/35359743 http://dx.doi.org/10.3389/fmicb.2022.836831 |
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author | Wong, Lilly M. Li, Dajiang Tang, Yuyang Méndez-Lagares, Gema Thompson, George R. Hartigan-O’Connor, Dennis J. Dandekar, Satya Jiang, Guochun |
author_facet | Wong, Lilly M. Li, Dajiang Tang, Yuyang Méndez-Lagares, Gema Thompson, George R. Hartigan-O’Connor, Dennis J. Dandekar, Satya Jiang, Guochun |
author_sort | Wong, Lilly M. |
collection | PubMed |
description | Human Immunodeficiency Virus-1 (HIV) remains a global health challenge due to the latent HIV reservoirs in people living with HIV (PLWH). Dormant yet replication competent HIV harbored in the resting CD4+ T cells cannot be purged by antiretroviral therapy (ART) alone. One approach of HIV cure is the “Kick and Kill” strategy where latency reversal agents (LRAs) have been implemented to disrupt latent HIV, expecting to eradicate HIV reservoirs by viral cytopathic effect or immune-mediated clearance. Protein Kinase C agonists (PKCa), a family of LRAs, have demonstrated the ability to disrupt latent HIV to an extent. However, the toxicity of PKCa remains a concern in vivo. Early growth response protein 1 (EGR1) is a downstream target of PKCa during latency reversal. Here, we show that PKCa induces EGR1 which directly drives Tat-dependent HIV transcription. Resveratrol, a natural phytoalexin found in grapes and various plants, induces Egr1 expression and disrupts latent HIV in several HIV latency models in vitro and in CD4+ T cells isolated from ART-suppressed PLWH ex vivo. In the primary CD4+ T cells, resveratrol does not induce immune activation at the dosage that it reverses latency, indicating that targeting EGR1 may be able to reverse latency and bypass PKCa-induced immune activation. |
format | Online Article Text |
id | pubmed-8960990 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89609902022-03-30 Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation Wong, Lilly M. Li, Dajiang Tang, Yuyang Méndez-Lagares, Gema Thompson, George R. Hartigan-O’Connor, Dennis J. Dandekar, Satya Jiang, Guochun Front Microbiol Microbiology Human Immunodeficiency Virus-1 (HIV) remains a global health challenge due to the latent HIV reservoirs in people living with HIV (PLWH). Dormant yet replication competent HIV harbored in the resting CD4+ T cells cannot be purged by antiretroviral therapy (ART) alone. One approach of HIV cure is the “Kick and Kill” strategy where latency reversal agents (LRAs) have been implemented to disrupt latent HIV, expecting to eradicate HIV reservoirs by viral cytopathic effect or immune-mediated clearance. Protein Kinase C agonists (PKCa), a family of LRAs, have demonstrated the ability to disrupt latent HIV to an extent. However, the toxicity of PKCa remains a concern in vivo. Early growth response protein 1 (EGR1) is a downstream target of PKCa during latency reversal. Here, we show that PKCa induces EGR1 which directly drives Tat-dependent HIV transcription. Resveratrol, a natural phytoalexin found in grapes and various plants, induces Egr1 expression and disrupts latent HIV in several HIV latency models in vitro and in CD4+ T cells isolated from ART-suppressed PLWH ex vivo. In the primary CD4+ T cells, resveratrol does not induce immune activation at the dosage that it reverses latency, indicating that targeting EGR1 may be able to reverse latency and bypass PKCa-induced immune activation. Frontiers Media S.A. 2022-03-10 /pmc/articles/PMC8960990/ /pubmed/35359743 http://dx.doi.org/10.3389/fmicb.2022.836831 Text en Copyright © 2022 Wong, Li, Tang, Méndez-Lagares, Thompson, Hartigan-O’Connor, Dandekar and Jiang. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Microbiology Wong, Lilly M. Li, Dajiang Tang, Yuyang Méndez-Lagares, Gema Thompson, George R. Hartigan-O’Connor, Dennis J. Dandekar, Satya Jiang, Guochun Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation |
title | Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation |
title_full | Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation |
title_fullStr | Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation |
title_full_unstemmed | Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation |
title_short | Human Immunodeficiency Virus-1 Latency Reversal via the Induction of Early Growth Response Protein 1 to Bypass Protein Kinase C Agonist-Associated Immune Activation |
title_sort | human immunodeficiency virus-1 latency reversal via the induction of early growth response protein 1 to bypass protein kinase c agonist-associated immune activation |
topic | Microbiology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8960990/ https://www.ncbi.nlm.nih.gov/pubmed/35359743 http://dx.doi.org/10.3389/fmicb.2022.836831 |
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