Human endogenous retrovirus HERV expression is not induced by treatment with the histone deacetylase HDAC inhibitors in cellular models of HIV-1 latencyReport as inadecuate




Human endogenous retrovirus HERV expression is not induced by treatment with the histone deacetylase HDAC inhibitors in cellular models of HIV-1 latency - Download this document for free, or read online. Document in PDF available to download.

Retrovirology

, 13:10

First Online: 06 February 2016Received: 14 September 2015Accepted: 28 January 2016

Abstract

BackgroundWhile 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.

ResultsIn 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.

ConclusionsWe 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.

KeywordsHDAC inhibitors HIV-1 latency HIV-1 cure Endogenous retroviruses HERV-K HML-2 AbbreviationsHDAChistone deacetylase

HERVhuman endogenous retrovirus

LTRlong terminal repeat

John Frater and Gkikas Magiorkinis contributed equally to this work

Electronic supplementary materialThe online version of this article doi:10.1186-s12977-016-0242-4 contains supplementary material, which is available to authorized users.

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Author: Tara Hurst - Matthew Pace - Aris Katzourakis - Rodney Phillips - Paul Klenerman - John Frater - Gkikas Magiorkinis

Source: https://link.springer.com/article/10.1186/s12977-016-0242-4



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