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Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal
The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models,...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Public Library of Science
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844474/ https://www.ncbi.nlm.nih.gov/pubmed/31710657 http://dx.doi.org/10.1371/journal.pone.0224879 |
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author | Trypsteen, Wim White, Cory H. Mukim, Amey Spina, Celsa A. De Spiegelaere, Ward Lefever, Steve Planelles, Vicente Bosque, Alberto Woelk, Christopher H. Vandekerckhove, Linos Beliakova-Bethell, Nadejda |
author_facet | Trypsteen, Wim White, Cory H. Mukim, Amey Spina, Celsa A. De Spiegelaere, Ward Lefever, Steve Planelles, Vicente Bosque, Alberto Woelk, Christopher H. Vandekerckhove, Linos Beliakova-Bethell, Nadejda |
author_sort | Trypsteen, Wim |
collection | PubMed |
description | The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models, we identified lncRNAs dysregulated in latency. PVT1 and RP11-347C18.3 were up-regulated in common between the two models, and RP11-539L10.2 was down-regulated. The major component of the latent HIV reservoir, memory CD4+ T-cells, had higher expression of these lncRNAs, compared to naïve T-cells. Guilt-by-association analysis demonstrated that lncRNAs dysregulated in latency were associated with several cellular pathways implicated in HIV latency establishment and maintenance: proteasome, spliceosome, p53 signaling, and mammalian target of rapamycin (MTOR). PVT1, RP11-347C18.3, and RP11-539L10.2 were down-regulated by latency reversing agents, suberoylanilide hydroxamic acid and Romidepsin, suggesting that modulation of lncRNAs is a possible secondary mechanism of action of these compounds. These results will facilitate prioritization of lncRNAs for evaluation as targets for HIV latency reversal. Importantly, our study provides insights into regulatory function of lncRNA during latent HIV infection. |
format | Online Article Text |
id | pubmed-6844474 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-68444742019-11-15 Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal Trypsteen, Wim White, Cory H. Mukim, Amey Spina, Celsa A. De Spiegelaere, Ward Lefever, Steve Planelles, Vicente Bosque, Alberto Woelk, Christopher H. Vandekerckhove, Linos Beliakova-Bethell, Nadejda PLoS One Research Article The latent cellular reservoir of HIV is recognized as the major barrier to cure from HIV infection. Long non-coding RNAs (lncRNAs) are more tissue and cell type-specific than protein coding genes, and may represent targets of choice for HIV latency reversal. Using two in vitro primary T-cell models, we identified lncRNAs dysregulated in latency. PVT1 and RP11-347C18.3 were up-regulated in common between the two models, and RP11-539L10.2 was down-regulated. The major component of the latent HIV reservoir, memory CD4+ T-cells, had higher expression of these lncRNAs, compared to naïve T-cells. Guilt-by-association analysis demonstrated that lncRNAs dysregulated in latency were associated with several cellular pathways implicated in HIV latency establishment and maintenance: proteasome, spliceosome, p53 signaling, and mammalian target of rapamycin (MTOR). PVT1, RP11-347C18.3, and RP11-539L10.2 were down-regulated by latency reversing agents, suberoylanilide hydroxamic acid and Romidepsin, suggesting that modulation of lncRNAs is a possible secondary mechanism of action of these compounds. These results will facilitate prioritization of lncRNAs for evaluation as targets for HIV latency reversal. Importantly, our study provides insights into regulatory function of lncRNA during latent HIV infection. Public Library of Science 2019-11-11 /pmc/articles/PMC6844474/ /pubmed/31710657 http://dx.doi.org/10.1371/journal.pone.0224879 Text en https://creativecommons.org/publicdomain/zero/1.0/ This is an open access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 (https://creativecommons.org/publicdomain/zero/1.0/) public domain dedication. |
spellingShingle | Research Article Trypsteen, Wim White, Cory H. Mukim, Amey Spina, Celsa A. De Spiegelaere, Ward Lefever, Steve Planelles, Vicente Bosque, Alberto Woelk, Christopher H. Vandekerckhove, Linos Beliakova-Bethell, Nadejda Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal |
title | Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal |
title_full | Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal |
title_fullStr | Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal |
title_full_unstemmed | Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal |
title_short | Long non-coding RNAs and latent HIV – A search for novel targets for latency reversal |
title_sort | long non-coding rnas and latent hiv – a search for novel targets for latency reversal |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6844474/ https://www.ncbi.nlm.nih.gov/pubmed/31710657 http://dx.doi.org/10.1371/journal.pone.0224879 |
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