title: Human endogenous retrovirus (HERV) expression is not induced by treatment with the histone deacetylase (HDAC) inhibitors in cellular models of HIV-1 latency.
abstract: 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.
authors: Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. tara.hurst@zoo.ox.ac.uk.
authors: Tara
authors: T
authors: Hurst
authors: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford, UK. matthew.pace@ndm.ox.ac.uk.
authors: Matthew
authors: M
authors: Pace
authors: Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. aris.katzourakis@zoo.ox.ac.uk.
authors: Aris
authors: A
authors: Katzourakis
authors: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford, UK. rodney.phillips@unsw.edu.au.|Faculty of Medicine, University of New South Wales, Sydney, Australia. rodney.phillips@unsw.edu.au.
authors: Rodney
authors: R
authors: Phillips
authors: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford, UK. paul.klenerman@medawar.ox.ac.uk.
authors: Paul
authors: P
authors: Klenerman
authors: Nuffield Department of Clinical Medicine, Peter Medawar Building for Pathogen Research, John Radcliffe Hospital, Oxford, UK. john.frater@ndm.ox.ac.uk.|Institute for Emerging Infections, The Oxford Martin School, Oxford, UK. john.frater@ndm.ox.ac.uk.|Oxford National Institute of Health Research Biomedical Research Centre, University of Oxford, Oxford, UK. john.frater@ndm.ox.ac.uk.
authors: John
authors: J
authors: Frater
authors: Department of Zoology, University of Oxford, South Parks Road, Oxford, UK. gkikas.magiorkinis@zoo.ox.ac.uk.
authors: Gkikas
authors: G
authors: Magiorkinis
mesh_terms: D002460:Cell Line; D020077:Endogenous Retroviruses / Q000187:drug effects* / Q000502:physiology*; D015686:Gene Products, env / Q000032:analysis / Q000235:genetics; D015684:Gene Products, pol / Q000032:analysis / Q000235:genetics; D015497:HIV-1 / Q000187:drug effects*; D056572:Histone Deacetylase Inhibitors / Q000378:metabolism*; D006801:Humans; D009000:Monocytes / Q000187:drug effects / Q000821:virology; D011533:Proviruses / Q000187:drug effects* / Q000502:physiology*; D013601:T-Lymphocytes / Q000187:drug effects / Q000821:virology; D014158:Transcription, Genetic; D014775:Virus Activation / Q000187:drug effects*
chemical_list: D015686:Gene Products, env; D015684:Gene Products, pol; D056572:Histone Deacetylase Inhibitors