MENU ▼
Read by QxMD icon Read
search
OPEN IN READ APP
JOURNAL ARTICLE

Reactivation of latent HIV-1 by new semi-synthetic ingenol esters

Diego Pandeló José, Koen Bartholomeeusen, Rodrigo Delvecchio da Cunha, Celina Monteiro Abreu, Jan Glinski, Thais Barbizan Ferreira da Costa, Ana Flávia Mello Bacchi Rabay, Luiz Francisco Pianowski Filho, Lech W Dudycz, Udaykumar Ranga, Boris Matija Peterlin, Luiz Francisco Pianowski, Amilcar Tanuri, Renato Santana Aguiar
Virology 2014, 462: 328-39
25014309
The ability of HIV to establish long-lived latent infection is mainly due to transcriptional silencing of viral genome in resting memory T lymphocytes. Here, we show that new semi-synthetic ingenol esters reactivate latent HIV reservoirs. Amongst the tested compounds, 3-caproyl-ingenol (ING B) was more potent in reactivating latent HIV than known activators such as SAHA, ingenol 3,20-dibenzoate, TNF-α, PMA and HMBA. ING B activated PKC isoforms followed by NF-κB nuclear translocation. As virus reactivation is dependent on intact NF-κB binding sites in the LTR promoter region ING B, we have shown that. ING B was able to reactivate virus transcription in primary HIV-infected resting cells up to 12 fold and up to 25 fold in combination with SAHA. Additionally, ING B promoted up-regulation of P-TEFb subunits CDK9/Cyclin T1. The role of ING B on promoting both transcription initiation and elongation makes this compound a strong candidate for an anti-HIV latency drug combined with suppressive HAART.

Comments

You need to log in or sign up for an account to be able to comment.

No comments yet, be the first to post one!

Related Papers

Available on the App Store

Available on the Play Store
Remove bar
Read by QxMD icon Read
25014309
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"