Abstract：
:Cells harboring latent HIV-1 pose a major obstacle to eradication of the virus. The 'shock and kill' strategy has been broadly explored to purge the latent reservoir; however, none of the current latency-reversing agents (LRAs) can safely and effectively activate the latent virus in patients. In this study, we report an ingenol derivative called EK-16A, isolated from the traditional Chinese medicinal herb Euphorbia kansui, which displays great potential in reactivating latent HIV-1. A comparison of the doses used to measure the potency indicated EK-16A to be 200-fold more potent than prostratin in reactivating HIV-1 from latently infected cell lines. EK-16A also outperformed prostratin in ex vivo studies on cells from HIV-1-infected individuals, while maintaining minimal cytotoxicity effects on cell viability and T cell activation. Furthermore, EK-16A exhibited synergy with other LRAs in reactivating latent HIV-1. Mechanistic studies indicated EK-16A to be a PKCγ activator, which promoted both HIV-1 transcription initiation by NF-κB and elongation by P-TEFb signal pathways. Further investigations aimed to add this compound to the therapeutic arsenal for HIV-1 eradication are in the pipeline.
journal_name
Sci Repjournal_title
Scientific reportsauthors
Wang P,Lu P,Qu X,Shen Y,Zeng H,Zhu X,Zhu Y,Li X,Wu H,Xu J,Lu H,Ma Z,Zhu Hdoi
10.1038/s41598-017-07157-0subject
Has Abstractpub_date
2017-08-25 00:00:00pages
9451issue
1issn
2045-2322pii
10.1038/s41598-017-07157-0journal_volume
7pub_type
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