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AHR is a tunable knob that controls HTLV-1 latency-reactivation switching
Establishing latent infection but retaining the capability to reactivate in certain circumstance is an ingenious tactic for retroviruses to persist in vivo while evading host immune surveillance. Many evidences indicate that Human T-cell leukemia virus type 1 (HTLV-1) is not completely silent in viv...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367443/ https://www.ncbi.nlm.nih.gov/pubmed/32678826 http://dx.doi.org/10.1371/journal.ppat.1008664 |
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author | Hong, Weihao Cheng, Wenzhao Zheng, Tingjin Jiang, Nan Xu, Ruian |
author_facet | Hong, Weihao Cheng, Wenzhao Zheng, Tingjin Jiang, Nan Xu, Ruian |
author_sort | Hong, Weihao |
collection | PubMed |
description | Establishing latent infection but retaining the capability to reactivate in certain circumstance is an ingenious tactic for retroviruses to persist in vivo while evading host immune surveillance. Many evidences indicate that Human T-cell leukemia virus type 1 (HTLV-1) is not completely silent in vivo. However, signals that trigger HTLV-1 latency-reactivation switching remain poorly understood. Here, we show that aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a critical role in HTLV-1 plus-strand expression. Importantly, HTLV-1 reactivation could be tunably manipulated by modulating the level of AHR ligands. Mechanistically, activated AHR binds to HTLV-1 LTR dioxin response element (DRE) site (CACGCATAT) and drives plus-strand transcription. On the other hand, persistent activation of nuclear factor kappa B (NF-κB) pathway constitutes one key prerequisite for AHR overexpression in HTLV-1 infected T-cells, setting the stage for the advent of AHR signaling. Our findings suggest that HTLV-1 might achieve its reactivation in vivo when encountering environmental, dietary, microbial and metabolic cues that induce sufficient AHR signaling. |
format | Online Article Text |
id | pubmed-7367443 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-73674432020-08-05 AHR is a tunable knob that controls HTLV-1 latency-reactivation switching Hong, Weihao Cheng, Wenzhao Zheng, Tingjin Jiang, Nan Xu, Ruian PLoS Pathog Research Article Establishing latent infection but retaining the capability to reactivate in certain circumstance is an ingenious tactic for retroviruses to persist in vivo while evading host immune surveillance. Many evidences indicate that Human T-cell leukemia virus type 1 (HTLV-1) is not completely silent in vivo. However, signals that trigger HTLV-1 latency-reactivation switching remain poorly understood. Here, we show that aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor, plays a critical role in HTLV-1 plus-strand expression. Importantly, HTLV-1 reactivation could be tunably manipulated by modulating the level of AHR ligands. Mechanistically, activated AHR binds to HTLV-1 LTR dioxin response element (DRE) site (CACGCATAT) and drives plus-strand transcription. On the other hand, persistent activation of nuclear factor kappa B (NF-κB) pathway constitutes one key prerequisite for AHR overexpression in HTLV-1 infected T-cells, setting the stage for the advent of AHR signaling. Our findings suggest that HTLV-1 might achieve its reactivation in vivo when encountering environmental, dietary, microbial and metabolic cues that induce sufficient AHR signaling. Public Library of Science 2020-07-17 /pmc/articles/PMC7367443/ /pubmed/32678826 http://dx.doi.org/10.1371/journal.ppat.1008664 Text en © 2020 Hong 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. |
spellingShingle | Research Article Hong, Weihao Cheng, Wenzhao Zheng, Tingjin Jiang, Nan Xu, Ruian AHR is a tunable knob that controls HTLV-1 latency-reactivation switching |
title | AHR is a tunable knob that controls HTLV-1 latency-reactivation switching |
title_full | AHR is a tunable knob that controls HTLV-1 latency-reactivation switching |
title_fullStr | AHR is a tunable knob that controls HTLV-1 latency-reactivation switching |
title_full_unstemmed | AHR is a tunable knob that controls HTLV-1 latency-reactivation switching |
title_short | AHR is a tunable knob that controls HTLV-1 latency-reactivation switching |
title_sort | ahr is a tunable knob that controls htlv-1 latency-reactivation switching |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7367443/ https://www.ncbi.nlm.nih.gov/pubmed/32678826 http://dx.doi.org/10.1371/journal.ppat.1008664 |
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