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Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency
BACKGROUND: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744380/ https://www.ncbi.nlm.nih.gov/pubmed/26852322 http://dx.doi.org/10.1186/s12977-016-0242-4 |
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author | Hurst, Tara Pace, Matthew Katzourakis, Aris Phillips, Rodney Klenerman, Paul Frater, John Magiorkinis, Gkikas |
author_facet | Hurst, Tara Pace, Matthew Katzourakis, Aris Phillips, Rodney Klenerman, Paul Frater, John Magiorkinis, Gkikas |
author_sort | Hurst, Tara |
collection | PubMed |
description | BACKGROUND: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences. RESULTS: In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin-1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells. CONCLUSIONS: We show that HDAC inhibitors did not substantially increase the transcription of the analysed HERV env or pol genes, suggesting that histone acetylation is not crucial for controlling HERV expression in these experimental models and in ex vivo primary human T cells. Importantly, this indicates that unwanted HERV expression does not appear to be a barrier to the use of HDAC inhibitors in HIV-1 cure strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0242-4) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-4744380 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-47443802016-02-07 Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency Hurst, Tara Pace, Matthew Katzourakis, Aris Phillips, Rodney Klenerman, Paul Frater, John Magiorkinis, Gkikas Retrovirology Research BACKGROUND: While antiretroviral therapies have improved life expectancy and reduced viral loads in HIV-1-positive individuals, the cessation of treatment results in a rebound of viral replication. This suggests that a reservoir of latently-infected cells remains within these patients, the identity of which is ill-defined and therefore difficult to target therapeutically. Current strategies are aimed at using drugs such as histone deacetylase (HDAC) inhibitors to induce the expression of latent HIV-1 proviruses in order to activate and ultimately eradicate this reservoir of infected cells. One concern with the use of HDAC inhibitors is that they could up-regulate human endogenous retroviruses (HERVs), as well as HIV-1, with potentially pathophysiological consequences. RESULTS: In this study, we analysed the transcription of HERV genes in HIV-1 latency T cell (J-LAT 8.4) and monocyte (U1) models following treatment with the HDAC inhibitors, vorinostat, panobinostat and romidepsin. We examined the expression of HERV-K (HML-2) env and pol, as well as the co-opted genes HERV-W env (syncytin-1), HERV-FRD env (syncytin-2), in these cell lines. Finally, we investigated HERV expression in primary human T cells. CONCLUSIONS: We show that HDAC inhibitors did not substantially increase the transcription of the analysed HERV env or pol genes, suggesting that histone acetylation is not crucial for controlling HERV expression in these experimental models and in ex vivo primary human T cells. Importantly, this indicates that unwanted HERV expression does not appear to be a barrier to the use of HDAC inhibitors in HIV-1 cure strategies. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12977-016-0242-4) contains supplementary material, which is available to authorized users. BioMed Central 2016-02-06 /pmc/articles/PMC4744380/ /pubmed/26852322 http://dx.doi.org/10.1186/s12977-016-0242-4 Text en © Hurst et al. 2016 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Hurst, Tara Pace, Matthew Katzourakis, Aris Phillips, Rodney Klenerman, Paul Frater, John Magiorkinis, Gkikas Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency |
title | Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency |
title_full | Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency |
title_fullStr | Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency |
title_full_unstemmed | Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency |
title_short | Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency |
title_sort | human endogenous retrovirus (herv) expression is not induced by treatment with the histone deacetylase (hdac) inhibitors in cellular models of hiv-1 latency |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4744380/ https://www.ncbi.nlm.nih.gov/pubmed/26852322 http://dx.doi.org/10.1186/s12977-016-0242-4 |
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