The histone deacetylase inhibitor ITF2357 decreases surface CXCR4 and CCR5 expression on CD4(+) T-cells and monocytes and is superior to valproic acid for latent HIV-1 expression in vitro

组蛋白去乙酰化酶抑制剂 ITF2357 可降低 CD4(+) T 细胞和单核细胞表面 CXCR4 和 CCR5 的表达,在体外抑制潜伏 HIV-1 表达方面优于丙戊酸

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作者:Shay Matalon, Brent E Palmer, Marcel F Nold, Antonio Furlan, Afework Kassu, Gianluca Fossati, Paolo Mascagni, Charles A Dinarello

Conclusion

ITF2357 is superior to VPA in inducing HIV-1 from latently infected cells. Safely used in humans, ITF2357 is an attractive candidate for HIV-1 clinical purging.

Methods

Latently infected cell lines were incubated with either ITF2357 or VPA and p24 levels were measured. Peripheral blood mononuclear cells of uninfected donors were treated with ITF2357 and HIV-1 coreceptors expression was assessed by flow cytometry.

Results

At clinically relevant concentrations, ITF2357 increased p24 by 15-fold in ACH2 cells and by 9-fold in U1 cells, whereas VPA increased expression less than 2-fold. Analogues of ITF2357 primarily targeting HDAC-1 increased p24 up to 30-fold. In CD4(+) T cells treated with ITF2357, CXCR4 expression decreased by 54% (P < 0.001).

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