Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes

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The advent of antiretroviral therapy has greatly improved the prognosis for HIV-infected individuals with access to care. However, current therapies are unable to cure infection, committing treated individuals to a lifetime of medication with significant economic burden. Furthermore, it has become clear that antiretroviral therapy does not completely restore health, leaving treated HIV-infected individuals at increased risk of cardiovascular disease, neurological disorders, and other health issues. Thus, there is a need to develop therapies capable of curing HIV infection. It is thought that, to be successful, curative strategies will need to combine a means to flush the virus out of the latently-infected cells in which it hides, with a means to kill these unmasked targets. A front-running approach proposes to use a class of drugs called histone deacetylase inhibitors (HDACis) as flushing agents, with cytotoxic T-lymphocytes (CTL, or killer T-cells) to purge viral reservoirs. Here, we uncover an unexpected negative interaction between these two agents, whereby HDACis suppress the ability of CTL to kill HIV-infected cells. This interaction has the potential to limit the effectiveness of combining CTL with HDACis in flush and kill approaches to HIV eradication, and should be considered in the prioritization and optimization of potential curative strategies.

Vyšlo v časopise: Histone Deacetylase Inhibitors Impair the Elimination of HIV-Infected Cells by Cytotoxic T-Lymphocytes. PLoS Pathog 10(8): e32767. doi:10.1371/journal.ppat.1004287
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1004287

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