Fig. 1.

KRIBB11 reveals differences in latency reversal in immortalized vs. primary T cells. In immortalized J-Lat cells, KRIBB11 can block the latency-reversing abilities of most LRAs (bryostatin, panobinostat, romidepsin, HBB2, bortezomib, and PMA/I) by inhibiting the recruitment of CycT1, which partners with HSF1 to induce HIV-1 transcription elongation. In patient cells, chemical stressors (disulfiram, HBB2, bortezomib, tricyclic bis[cyano enone] [TBE-31], and Shikonin) known to activate HSF1 are unable to reverse HIV-1 latency, perhaps due to low levels of CycT1 in primary cells compared with J-Lats. By contrast, PMA/I reactivates HIV-1 by increasing the expression of CycT1. As a result, KRIBB11 is able to inhibit PMA/I’s LRA function.