Avtor/Urednik		José, Diego Pandeló; Bartholomeeusen, Koen; da Cunha, Rodrigo Delvecchio; Monteiro Abreu, Celina; Gliński, Jan; Ferreira da Costa, Thais Barbizan; Bacchi Rabay, Ana Flávia Mello; Pianowski Filho, Luiz Francisco; Dudycz, Lech W.; Peterlin, Matija Boris
Naslov		Reactivation of latent HIV-1 by new semi-synthetic ingeol esters
Tip		članek
Vol. in št.		Letnik 462/463
Leto izdaje		2014
Obseg		str. 328-339
ISSN		0042-6822 - Virology
Jezik		eng
Abstrakt		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-alpha, PMA and HMBA. ING B activated PKC isoforms followed by NF-kappaB nuclear translocation. As virus reactivation is dependent on intact NF-kappaB 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.
Proste vsebinske oznake		HIV latency resting cells HIV latentnost mirujoče celice