Short report
"Shock and kill" effects of class I-selective histone deacetylase inhibitors in combination with the glutathione synthesis inhibitor buthionine sulfoximine in cell line models for HIV-1 quiescence
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* Corresponding author: Andrea Savarino andrea.savarino@iss.it
- † Equal contributors
1 Dept of Infectious, Parasitic and Immune-mediated Diseases, Istituto Superiore di Sanità , Viale Regina Elena, 299, 00161, Rome, Italy
2 Pasteur Institute, Cenci-Bolognetti Foundation, Dept of Drug Chemistry and Technologies, Sapienza University of Rome, P.le A. Moro, 5, 00185, Rome, Italy
3 Dept of General Pathology, 2nd University of Naples, Vico L. De Crecchio 7, 80138 Naples, Italy
4 Pasteur Institute, Cenci-Bolognetti Foundation, Dept of Public Health Sciences, Sapienza University of Rome, P.le A. Moro, 5, 00185, Rome, Italy
5 Dept of Experimental Medicine, University of Rome Tor Vergata, Rome, Italy
6 IRCCS San Raffaele Pisana, via della Pisana 235, 00163 Rome, Italy
Retrovirology 2009, 6:52 doi:10.1186/1742-4690-6-52
Published: 2 June 2009Additional files
Additional file 1:
Structures and HDAC inhibiting activity of the cited HDACIs. Where data on human HDACs are unavailable, data on maize HD1-B (homologous with human class I HDACs) and HD1-A (homologous with human class II HDACs), or relevant references, are provided.
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Additional file 2:
To study the HDACI response in a cell population, we used quiescently infected T-lymphoid Jurkat cell clones. Two types of cell clones were used: 1) A1, and A2, which have an integrated GFP/Tat construct under control of the HIV-1 LTR; 2) 6.3, and 8.4, which contain the entire HIV-1 genome under control of the LTR and have the GFP gene replacing nef. The 6.3 cells display insignificant basal levels of GFP expression. Cells were incubated with the different treatments, and GFP expression was monitored in gated live cells at 12, 24 and 72 hours by standard flow cytometric techniques. Results are presented as fluorescence histograms. Each histogram reports the percentage of fluorescent cells beyond a threshold value established using non-infected Jurkat cells.
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Additional file 3:
Structural superimposition of MC2211 (carbon backbone in cyan) and SAHA (vorinostat; carbon backbone in yellow) docking at the HDAC2 catalytic site. SAHA, a non-selective HDACI, displays an amide group in a conformation that does not match that of the class I-selective HDACIs (Figure 3). The other molecular players are displayed in the same fashion as in Figure 3.
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