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Micro RNA targets in HIV latency: Insights into novel layers of latency control

Micro RNA targets in HIV latency: Insights into novel layers of latency control
Micro RNA targets in HIV latency: Insights into novel layers of latency control
Despite the considerable progress that has been made in identifying cellular factors and pathways that contribute to establishment and maintenance of the latent HIV reservoir, it remains the major obstacle to eradicating this virus. Most recently, noncoding genes have been implicated in regulation of HIV expression. In this study, small RNA sequencing was used to profile expression of microRNAs (miRNAs) in a primary CD4+ T cell in vitro model of HIV latency. Previously, we have shown that protein-coding genes dysregulated in this model were enriched for the p53 signaling pathway, which was confirmed experimentally. We further found a link between p53 signaling and dysregulated long noncoding RNAs. In this study, we hypothesized that miRNAs may provide an additional level of regulation of the p53 signaling pathway during HIV latency. Twenty-six miRNAs were identified to be dysregulated in our latency model. A subset of these miRNAs was validated by real-time quantitative polymerase chain reaction. Predicted messenger RNA (mRNA) targets and cellular pathways enriched for mRNA targets were identified using several analytical methods. Our analyses showed that many protein-coding genes and pathways targeted by dysregulated miRNAs have relevance to regulation of HIV expression or establishment of HIV latency. The p53 signaling pathway was found among pathways that were targeted by dysregulated miRNAs at a greater level than expected by chance. This study provides a mechanistic insight into regulation of the p53 pathway through miRNAs that may contribute to the establishment of latency.
HIV latency, RNA-Seq, miRNA, microRNA, p53 signaling, small RNA sequencing
0889-2229
Heinson, Ashley
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Woo, Jeongmin
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Mukim, Amey
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White, Cory H
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Moesker, Bastiaan
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Bosque, Alberto
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Spina, Celsa A.
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Woelk, Christopher
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Macarthur, Benjamin
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Beliakova-Bethell, Nadejda
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Heinson, Ashley
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Woo, Jeongmin
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Mukim, Amey
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White, Cory H
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Moesker, Bastiaan
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Bosque, Alberto
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Spina, Celsa A.
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Woelk, Christopher
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Macarthur, Benjamin
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Beliakova-Bethell, Nadejda
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Heinson, Ashley, Woo, Jeongmin, Mukim, Amey, White, Cory H, Moesker, Bastiaan, Bosque, Alberto, Spina, Celsa A., Woelk, Christopher, Macarthur, Benjamin and Beliakova-Bethell, Nadejda (2020) Micro RNA targets in HIV latency: Insights into novel layers of latency control. AIDS Research and Human Retroviruses. (doi:10.1089/aid.2020.0150).

Record type: Article

Abstract

Despite the considerable progress that has been made in identifying cellular factors and pathways that contribute to establishment and maintenance of the latent HIV reservoir, it remains the major obstacle to eradicating this virus. Most recently, noncoding genes have been implicated in regulation of HIV expression. In this study, small RNA sequencing was used to profile expression of microRNAs (miRNAs) in a primary CD4+ T cell in vitro model of HIV latency. Previously, we have shown that protein-coding genes dysregulated in this model were enriched for the p53 signaling pathway, which was confirmed experimentally. We further found a link between p53 signaling and dysregulated long noncoding RNAs. In this study, we hypothesized that miRNAs may provide an additional level of regulation of the p53 signaling pathway during HIV latency. Twenty-six miRNAs were identified to be dysregulated in our latency model. A subset of these miRNAs was validated by real-time quantitative polymerase chain reaction. Predicted messenger RNA (mRNA) targets and cellular pathways enriched for mRNA targets were identified using several analytical methods. Our analyses showed that many protein-coding genes and pathways targeted by dysregulated miRNAs have relevance to regulation of HIV expression or establishment of HIV latency. The p53 signaling pathway was found among pathways that were targeted by dysregulated miRNAs at a greater level than expected by chance. This study provides a mechanistic insight into regulation of the p53 pathway through miRNAs that may contribute to the establishment of latency.

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More information

Accepted/In Press date: 12 October 2020
e-pub ahead of print date: 10 November 2020
Keywords: HIV latency, RNA-Seq, miRNA, microRNA, p53 signaling, small RNA sequencing

Identifiers

Local EPrints ID: 445650
URI: http://eprints.soton.ac.uk/id/eprint/445650
ISSN: 0889-2229
PURE UUID: cb984b22-eadc-4e50-a13e-78ec2d336413

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Date deposited: 05 Jan 2021 17:31
Last modified: 25 Nov 2021 20:37

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Contributors

Author: Ashley Heinson
Author: Jeongmin Woo
Author: Amey Mukim
Author: Cory H White
Author: Bastiaan Moesker
Author: Alberto Bosque
Author: Celsa A. Spina
Author: Christopher Woelk
Author: Nadejda Beliakova-Bethell

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