Discovering the Mechanisms of Wikstroelide E as a Potential HIV-Latency-Reversing Agent by Transcriptome Profiling

The discovery of efficient and specific HIV-latency-reversing agents is critical for HIV therapy. Here, we developed wikstroelide E, a daphnane diterpene from the buds of Wikstroemia chamaedaphne, as a potential HIV-latency-reversing agent that is 2500-fold more potent than the drug prostratin. Based on transcriptome analysis, the underlying mechanism was that wikstroelide E regulated the MAPK, PI3K-Akt, JAK-Stat, TNF, and NF-kappa B signaling pathways. We clearly demonstrated that wikstroelide E reversed latent HIV infection by activating PKC-NF-kappa B signals, serving as a proxy for verifying the transcriptome data. Strikingly, the Tat protein contributes to the robust activation of latent HIV in wikstroelide-E-treated cells, producing an unexpected latency-reversing effect against latent HIV. This study provides the basis for the potential development of wikstroelide E as an effective HIV-latency-reversing agent.

Automated summary

Wikstroelide E is a potential HIV-latency-reversing agent that is 2500-fold more potent than prostratin. It reverses latent HIV infection by regulating multiple signaling pathways, with the Tat protein contributing to its robust activation of latent HIV. This study lays the foundation for the potential development of Wikstroelide E as an effective HIV-latency-reversing agent.