FIG. 2.

Natural products that activate HIV transcription. Natural product-derived compounds have been studied, which reactivate latent HIV by inducing HIV transcription. (A) PKC agonist (bryostatin, prostratin, and ingenol), a crude extract of kansui and procyanidin, activate cellular NF-κB, which contributes to transcription initiation. (B) PKC agonist (bryostatin, prostratin, and ingenol), a crude extract of kansui, and procyanidin induce cellular expression of CycT1, part of the P-TEFb complex. (C) Increase in total CycT1 permits HDACi and BET-bromodomain inhibitors to function by activating P-TEFb and releasing it from its inactive complex with Hexim1:7SK. Altogether, increase in expression and release of free P-TEFb allow recruitment of P-TEFb to NF-κB and POLII, resulting in transcription elongation. (D) A crude extract of kansui further reactivates latent HIV by increasing cellular expression of CDK11, which complexes with CycL to promote cleavage and polyadenylation (CPA) recruitment and proper mRNA end processing. NF-κB, nuclear factor kappa B; PKC, protein kinase C; P-TEFb, positive transcription elongation factor b.