Discovering the Mechanisms of Wikstroelide E as a Potential HIV-Latency-Reversing Agent by Transcriptome Profiling.
Shi-Fei LiXue LiangXing-Kang WuXiang GaoLi-Wei ZhangPublished in: Journal of natural products (2021)
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-κB signaling pathways. We clearly demonstrated that wikstroelide E reversed latent HIV infection by activating PKC-NF-κB 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.
Keyphrases
- antiretroviral therapy
- hiv positive
- hiv infected
- signaling pathway
- hiv testing
- human immunodeficiency virus
- pi k akt
- hepatitis c virus
- hiv aids
- men who have sex with men
- cell cycle arrest
- induced apoptosis
- south africa
- gene expression
- rheumatoid arthritis
- oxidative stress
- genome wide
- cell proliferation
- immune response
- single cell
- risk assessment
- stem cells
- inflammatory response
- small molecule
- rna seq
- dna methylation
- cell therapy
- artificial intelligence