HMBA Enhances Prostratin-Induced Activation of Latent HIV-1 via Suppressing the Expression of Negative Feedback Regulator A20/TNFAIP3 in NF-κB Signaling

Figure 1

HMBA and prostratin synergistically antagonize HIV-1 latency in J-Lat T-lymphocytes by activating both transcriptional initiation and elongation. (a to c) HMBA and prostratin synergistically activate the replication of latent HIV-1 proviruses. J-Lat clones A2, 9.2, and 2D10 were treated with indicated pharmacological compounds. GFP expression was measured by flow cytometry. The percentage of GFP positive cells is presented to reflect the transcriptional activation of the latent HIV proviruses. (d) HMBA and prostratin synergistically activate HIV-LTR-Luc expression. HeLa cells with integrated HIV-LTR-luciferase reporter gene (HIV-LTR-Luc) were treated with indicated compounds. The cell lysates were prepared for luciferase assay for the expression of HIV-LTR-Luc. (e) HMBA and prostratin synergistically activate both transcriptional initiation and elongation of HIV-1. HIV-LTR-Luc cells were treated with indicated compounds. The isolated RNA was assayed by qRT-PCR for the initiation and elongation transcripts of HIV-LTR-Luc. The qRT-PCR fragments representing transcriptional initiation (+1~+59, TAR) and elongation (+468~+593, luciferase) are illustrated in top panel. For (d) and (e), data are presented as fold enhancement compared to untreated cells.

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