Histone deacetylase inhibitors have negative effects on the elimination of HIV-infected cells by cytotoxic T-Lymphocytes

 

Antiretroviral therapy (ART) has been used as an effective clinical strategy in suppressing HIV-induced viremia, however, it shows its limitations in curing infection because infected cells may undergo quiescent state which is invisible to immune system. Histone deacetylase inhibitors (HDACis) have been reported to force HIV expression in latent cells. Jones et al. tested the impact of three HDACis, suberanilohydroxamic acid (SAHA), romidepsin and panobinostat, in clinical development on immune effectors functions, such as T-cell effector. The article was published on PLoS One.

 

They found all three HDACis rapidly suppressed cytokine production of viable T-cells. In addition, romidepsin and panobinostat caused selective death of activated T-cells. Immune effectors, such as HIV-specific cytotoxic T-lymphocytes (CTL), is needed to recognize and eliminate these cells with exposed targets. HDACis impaired IFN-γ production mediated by CTL, and also the elimination of HIV-infected target cells. In the test, romidepsin had a greater effect on inhibition of antiviral function than SAHA and panobinostat. The findings indicated HDACis may induce unintended negative effect on the effector functions of CTL. They may be a critical consideration for therapeutic interruptions.

 

Reference:
PLoS Pathog. 2014 Aug 14;10(8):e1004287.

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S3020	Romidepsin	Romidepsin (FK228, Depsipeptide, FR 901228, NSC 630176) is a potent HDAC1 and HDAC2 inhibitor with IC50 of 36 nM and 47 nM in cell-free assays, respectively. Romidepsin (FK228/depsipeptide) controls growth and induces apoptosis in neuroblastoma tumor cells.
S1030	Panobinostat (LBH589)	Panobinostat (LBH589, NVP-LBH589) is a novel broad-spectrum HDAC inhibitor with IC50 of 5 nM in a cell-free assay. Panobinostat (LBH589) induces autophagy and apoptosis. Panobinostat effectively disrupts HIV latency in vivo. Phase 3.

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HDAC